ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Mast cell-derived mediators

Mast cell-derived mediators
Literature review current through: Jan 2024.
This topic last updated: May 26, 2022.

INTRODUCTION — Mast cells release various mediators upon activation, which are responsible for many of the systems of allergic disease and anaphylaxis. These mediators can be divided into three overlapping categories: preformed mediators, newly synthesized lipid mediators, and cytokines and chemokines.

This topic will review mast cell mediators. The information in this topic pertains to human mast cells whenever possible, and notation is made when data are derived purely from murine studies. The development, physiologic roles, surface receptors, and signal transduction of mast cells are reviewed separately. (See "Mast cells: Development, identification, and physiologic roles" and "Mast cells: Surface receptors and signal transduction".)

PREFORMED MEDIATORS — Mast cell secretory granules contain preformed mediators that are rapidly (within seconds to minutes) released into the extracellular environment upon cell stimulation. These mediators include histamine, neutral proteases, proteoglycans, and some cytokines, such as tumor necrosis factor-alpha (TNF-alpha). They are responsible for many of the acute signs and symptoms of mast cell-mediated allergic reactions, including edema, bronchoconstriction, and increased vascular permeability. Specific pharmacotherapy to inhibit and/or antagonize mast cell mediators is reviewed elsewhere.

Histamine — Histamine is produced predominantly by mast cells but also is elaborated by basophils, neutrophils [1], and platelets. It is stored in both scroll-like and lattice secretory granules of the human mast cell [2]. Human cutaneous mast cells are estimated to contain 1.9 micrograms of histamine per 106 cells [3]. Secretory granule exocytosis and release of histamine occurs rapidly after either immunoglobulin E (IgE)- or non-IgE-based stimulation [4]. The effects of histamine are mediated through H1, H2, H3, and H4 receptors located on target cells:

H1-mediated actions include increased venular permeability, bronchial and intestinal smooth muscle contraction, increased nasal mucus production, widened pulse pressure, increased heart rate and cardiac output, flushing, and T cell neutrophil and eosinophil chemotaxis [5,6]. In mice, lack of H1 receptors leads to reduced lung inflammation as a consequence of the decreased T cell influx [6].

The effects mediated through the H2 receptor include increased venular permeability, increased gastric acid secretion, and airway mucus production but inhibition of neutrophil and eosinophil influx [7,8].

An H3 receptor has been located in the brain, as well as on sympathetic nerve fibers innervating blood vessels in the nasal mucosa and heart, although its precise role is not fully characterized [9,10].

An H4 receptor has been identified and cloned in both mice and humans [11,12]. This receptor modulates T helper type 2 (Th2) responses, and H4-deficient mice have decreased lung inflammation with less infiltration of eosinophils and lymphocytes [13]. Acting through the H4 receptor, histamine can act as a chemoattractant for mouse bone marrow-derived mast cells and modulate calcium influx [14]. In humans, the actions of histamine at the H4 receptor provide a potent chemotactic pathway for human eosinophils [15].

Serotonin — Human mast cells produce the biogenic amine serotonin during fetal development and possibly under some conditions in adult life [16,17]. Human fetal periodental mast cells produce and store serotonin in high amounts, coinciding with the appearance of enameloblasts [16].

Proteoglycans — The metachromatic staining of mast cell granules is due to sulfated, anionic proteoglycans, such as heparin and chondroitin sulfate. These are composed of a peptide core, serglycin, to which is added the complex glycosaminoglycans [18,19].

Heparin may serve to stabilize the multimeric complex of histamine, proteoglycan, and active neutral proteases within the secretory granule [20]. With granule exocytosis, heparin retains many of the proteases in the macromolecular complex [21-23]. Heparin also functions as an anticoagulant, inhibits the complement cascade, and markedly potentiates the action of angiogenic factors, such as basic fibroblast growth factor [24-29].

Chondroitin sulfate-E, a highly sulfated proteoglycan like heparin, has kinin pathway activation effects and protease-stabilizing functions [30].

Tryptases and other proteases — Important mast cell proteases include the tryptases, chymases, cathepsin G, renin, and a mast cell-specific carboxypeptidase A [20].

Tryptases — Tryptases are the most abundant proteases of the human mast cell, comprising up to 20 percent of the cell protein [3,31,32]. Some human mast cells contain up to 35 micrograms of tryptase/106 cells, which is a dramatically higher protease content than any other granulocyte. The other cell type that contains some tryptase, the basophil, has only very low levels (0.4 percent of the tryptase in mast cells) [33]. Thus, serum tryptase is a relatively specific marker of mast cell degranulation/activation. The demonstration that a mast cell-mediated event has occurred is important in the diagnosis of mast cell disorders, anaphylaxis, and drug-allergic reactions. (See "Mast cell disorders: An overview" and "Anaphylaxis: Acute diagnosis", section on 'Laboratory tests' and "Perioperative anaphylaxis: Clinical manifestations, etiology, and management", section on 'Laboratory tests at the time of the reaction'.)  

Two forms of tryptase are used clinically: Total tryptase and mature tryptase. Total tryptase levels are detectable in normal donors at serum levels of up to 15 ng/mL and reflect total body mast cell content. Persistent elevations in total tryptase in excess of 20 ng/mL are indicative of systemic mastocytosis. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

By comparison, mature active tryptase is stored within the secretory granule and released only during exocytosis [34]. It requires the heparin proteoglycans for activity [20]. Serum levels of this form of tryptase are normally undetectable (<1 ng/mL). The normal ratio between total and mature tryptase is usually less than 20 [33].

Mature tryptase serves as a useful marker of mast cell degranulation, as it is a product nearly exclusive to mast cells. Elevations of mature tryptase may be observed during acute anaphylactic events involving severe symptoms and hypotension, rising within 15 minutes and detectable by 30 to 60 minutes after the event. Elevations can persist for several hours, depending upon the magnitude of the initial rise and can be associated with elevations of total tryptases. Elevations in mature beta tryptase can be used to confirm the diagnosis of anaphylaxis, although levels might not rise during food-induced anaphylaxis, possibly reflecting differences in the pathophysiology of these forms of anaphylaxis [35]. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)

Tryptase levels in the bronchoalveolar fluid correlate with asthma severity and in severe asthma, this correlation is independent of biomarkers of type 2 inflammation such as eosinophil and periostin levels. Genetic alleles that increase the activity of tryptase decrease the response to treatment with omalizumab [36]. This finding suggests that anti-tryptase drugs could be developed for severe asthma in the future.

Functions — The tryptases are serine-endopeptidases that exhibit trypsin-like activity and cleave after basic amino acid residues in the proteins [37]. They are cationic tetrameric proteins that form a macromolecular complex with heparin proteoglycan [38]. These complexes are distinct from those containing chymase and carboxypeptidase, implying separate pathways of protease processing [22].

Tryptase has been shown to have many actions in vitro, although the relative importance of these remains unclear [20]. These actions include:

Inactivation of fibrinogen and inhibition of fibrinogenesis, with anticoagulant activity that exceeds that of heparin. Beta tryptase, which is enzymatically active upon release from granules, degrades the alpha chain of fibrinogen and prevents its activation [39,40]. This may explain why some patients with anaphylaxis or mastocytosis develop hemorrhagic disorders (eg, abnormal intraoperative bleeding) and why children with diffuse cutaneous mastocytosis can bleed into the blisters.

Activation of tissue matrix metalloproteinases (MMP), including prostromelysin (MMP-3), which activates collagenase of rheumatoid synovial cells [41].

Inactivation of certain neuropeptides including the bronchodilatory vasoactive intestinal peptide (VIP) [42,43].

Stimulation of fibroblast proliferation and mRNA synthesis for procollagen in human culture systems [44,45].

Chemotactic activity for eosinophils [46]. Recruitment of eosinophils contributes to the late phase of an allergic reaction (or allergen challenge), which is important in disorders such as asthma. (See "Pathogenesis of asthma", section on 'Early and late phase reactions'.)

Upregulation of interleukin 8 (IL-8) synthesis and intercellular adhesion molecule-1 (ICAM-1) expression in bronchial epithelial cells [47].

A pruritogenic effect of tryptase has been found in mice through the proteinase-activated receptor-2 (PAR2) receptor [48]. Human mast cells also have PAR2 receptors, although further study in humans is needed.

Tryptase catalytic activity can trigger mast cell degranulation in a feedforward manner [36].

Several human mast cell phenotypes are delineated based upon the relative content of tryptase, chymase, and the mast cell-specific carboxypeptidase, CPA3 [3]:

MCTC (mast cells containing tryptase and chymase) – Contain both tryptase (in the greatest amounts) and chymase (skin and intestinal submucosa) and are the predominant type of MC found in connective tissue locations like the skin and around blood vessels. In the inflamed nasal tissue of patients with chronic rhinosinusitis, the MCTC acquire a pro-inflammatory phenotype with increased expression of chemokines (CCL2, CCL3, CCL4), growth factors (CSF1 and CSF2), and COX2 [49].

MCT (mast cells containing tryptase) – Contain tryptase but little chymase (mucosal tissues) and are associated with inflammation and found mostly in mucosa in the lung and intestine. Of note, this phenotype is T cell-dependent and is lost in patients with acquired immunodeficiency syndrome (AIDS) [50].

Although MCTs are the predominant epithelial phenotype associated with recruited mast cells in the setting of allergic inflammation, mast cells expressing both chymase and tryptase are found in the epithelium of patients with severe asthma, suggesting a switch in phenotype with more severe disease [51,52].

MCC (mast cells containing chymase) – Contain only chymase and are found in the intestine.

MCT-CPA (mast cells containing carboxypeptidase A) are a mucosal phenotype found in eosinophilic esophagitis and a subgroup of asthmatics characterized with high T helper type 2 (Th2) activity [53,54]. This subgroup contains only tryptase and CPA with little or no chymase. MCT-CPA are dramatically increased in polyps of patients with chronic rhinosinusitis. They notably also express IL17RB, the receptor for the cytokine IL-25 [49].

Carboxypeptidase A — Mast cell carboxypeptidase A (CPA3) may be the most specific mast cell marker identified, as it has not been identified in basophils, unlike tryptase. However, it is not readily found in serum and thus is not a marker that can be used to identify mast cell activation, except within tissue sections. It is primarily localized within the MCTC subset in gut submucosa and in skin [55-57]. Human foreskin mast cells are estimated to contain 16 micrograms of CPA per106 cells [58].

This exopeptidase is functionally similar to pancreatic carboxypeptidase B, even though it is more similar to pancreatic carboxypeptidase A by amino acid sequence. It functions at neutral to basic pH to cleave carboxy-terminal aliphatic and aromatic amino acids from proteins after their exposure to chymotryptic proteases [59]. CPA3 functions to convert angiotensin I to angiotensin II [59] and has been shown to degrade neuropeptides [60]. It may also degrade some toxins, such as those in bee and snake venoms [61,62].

Chymase — The MCTC (and rare MCC) subpopulations of human mast cells contain the chymotrypsin-like serine endopeptidase chymase and/or a second member of this gene family, cathepsin-G [55,57,59,63]. Cathepsin-G is also found in human neutrophils and eosinophils.

Mast cell chymase has the following activities:

A 100-fold greater potency in the conversion of angiotensin I to angiotensin II, compared with angiotensin-converting enzyme (ACE) [64]

Inactivation of bradykinin and the neuropeptides VIP and substance P [65,66]

Cleavage of laminin, type IV collagen, and fibronectin with attendant basement membrane degradation [67]

Converting the precursor of interleukin 1b (IL-1b) to an active form and stimulating secretion from airway serous cells [68,69]

Renin — Renin is a protease produced predominantly by juxtaglomerular cells in the kidney. However, significant local production of renin is also provided by cardiac mast cells [70,71]. Thus, mast cells provide both renin and ACE activity through chymase, both of which activate the renin-angiotensin system. It remains unclear whether this mechanism represents a protective response or if it contributes to ischemia-reperfusion injuries and predisposes to cardiac arrhythmias [72,73].

NEWLY SYNTHESIZED LIPID MEDIATORS — Mast cells utilize membrane phospholipids as a source of arachidonic acid for the synthesis of prostaglandins (PG), leukotrienes (LT), and platelet-activating factor (PAF) [74]. These inflammatory mediators are referred to as eicosanoids (ie, derived from arachidonic acid). The production of these mediators is initiated when phospholipase (PL) A2 enzymes release arachidonic acid from phospholipids. Arachidonate is converted to the intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and then to the epoxide, LTA4, by 5-lipoxygenase (5-LO). Subsequent conversion into the cysteinyl leukotriene LTC4 is achieved by LTC4 synthase or to the dihydroxy leukotriene LTB4 by LTA4 hydrolase [75].

Lipid mediators are formed de novo from membrane phospholipids after cell activation. In contrast to the preformed mediators, which are released immediately by exocytosis, lipid mediators appear more slowly, generally from 15 minutes to hours after activation, leading to their initial name of "slow reactive substance of anaphylaxis" (SRS-A). As a group, they are responsible for some of the signs and symptoms of allergic reactions, such as airflow obstruction, as well as leukocyte and dendritic cell recruitment. Not all degranulating stimuli will result in eicosanoid generation. Anaphylatoxins and neuropeptides activate mast cells in such a manner that minimal eicosanoids are produced [76-78].

Prostaglandins — Prostaglandin D2 (PGD2) is the principal prostaglandin produced by mast cells, and it has been recognized in bronchial or nasal secretions after allergen challenge [79,80]. The robust production of this mediator by mast cells makes it another good signature of mast cell activation. Its metabolite (9-alpha, 11-beta-PGF2) appears in the urine of patients with systemic mastocytosis and in aspirin-induced asthma [81,82]. Further support for its role in allergic reactions comes from mice lacking the PGD2 receptor, DP1, which showed decreased airway reactivity in a murine asthma model [83]. Salicylate therapy can be used to control PGD2 biosynthesis in these conditions. However, due to idiosyncratic responses to low doses of acetyl salicylate, such therapy must be initiated in a protected setting [82,84]. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis" and "Aspirin-exacerbated respiratory disease".)

Intradermal injection of PGD2 leads to a wheal-and-flare response due to vasodilation and increased vasopermeability [85], and inhalation of PGD2 causes airway smooth muscle bronchoconstriction [86]. PGD2 has been shown to inhibit platelet aggregation, be chemotactic for neutrophils, and activate eosinophils [87-89]. PGD2 has a potent sleep-inducing function, and when measured in rat cerebrospinal fluid, it was shown to have a circadian rhythm with elevated levels during sleep deprivation [90]. Whether mast cells contribute to brain levels of PGD2 is not known. Flushing in response to the drug niacin is mediated by PGD2 [91]. This adverse effect of niacin and measures to block PGD2 are reviewed separately. (See "Low-density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors", section on 'Nicotinic acid (niacin)'.)

Human mast cells from different tissues have variable capacities to generate eicosanoids. PGD2 and LTC4 appear to be generated in approximately equal amounts by mast cells from skin or lung in response to activation by immunoglobulin E (IgE) and antigen, whereas lung mast cells generate 10-fold more LTC4 than PGD2 [73,92].

Cysteinyl leukotrienes — Activated human mast cells produce the parent of the cysteinyl leukotrienes, LTC4, along with far lesser amounts of LTB4 [93]. The production of LTB4 by mouse mast cells has been implicated in the specific recruitment of T cells to the lung with allergic inflammation [94,95]. LTC4 undergoes carrier-mediated export and subsequent extracellular conversion to the receptor active metabolites, LTD4 and LTE4 [96]. Cysteinyl leukotrienes exert their effect through activation of three distinct receptors:

Cysteinyl leukotriene receptor 1 (CysLT1R) is the high affinity receptor for LTD4 and binds LTC4 and LTE4 with lesser affinity. CysLT1R mediates cysteinyl leukotriene-dependent smooth muscle constriction and is inhibited by the CysLT1R inhibitors montelukast, zafirlukast, pranlukast.

CysLT2R is resistant to montelukast and other CysLT1R antagonists and binds LTC4 and LTD4 equally. CysLT1R and CysLT2R are broadly expressed by structural and hematopoietic cells, including mast cells.

CysLT3R, also called OXGR1 or GPR99, is a high-affinity receptor for LTE4 and is predominantly an epithelial cell receptor [97].

The cysteinyl leukotrienes increase microvascular permeability and are potent inducers of long-lasting wheal-and-flare responses [98]. Upon inhalation, they elicit bronchoconstriction in normal subjects with more than 1000-fold greater potency than histamine [99,100]. Levels of cysteinyl leukotrienes or their metabolites are elevated in nasal secretions in allergic rhinitis, bronchoalveolar lavage and urine from asthmatics under various circumstances, and in venous effluent elicited from cold urticaria [101-104]. LTE4 may also be an autocrine factor for mast cells, increasing cell proliferation, survival, and secretion of PGD2 [105-107].

Drugs that block the production of cysteinyl leukotrienes (zileuton) or block the actions of these compounds at the receptor level (montelukast, zafirlukast, and others) are used in the management of asthma, allergic rhinitis, and some forms of drug hypersensitivity. (See "Antileukotriene agents in the management of asthma".)

Platelet-activating factor — Platelet-activating factor (PAF) is produced and secreted by stimulated mouse and human mast cells through the action of the enzyme phospholipase A2 [108,109]. PAF acts through a specific receptor to chemoattract eosinophils, neutrophils, monocytes, and macrophages [110-112] and to stimulate macrophage cytokine production [113]. At a tissue level, PAF causes bronchoconstriction and vasopermeability [114]. Endothelial PAF interacts with neutrophils, leading to changes in their integrin expression with binding to intercellular adhesion molecule-1 (ICAM-1) on the endothelial cell, thereby promoting neutrophil attachment and transmigration [115].

Deficiencies of PAF acetylhydrolase, an enzyme that inactivates PAF, have been linked to asthma in certain populations, as well as to severe anaphylaxis [116,117]. The PAF antagonist, Y24180, has been shown to improve pulmonary function in some asthmatics [118]. (See "Pathophysiology of anaphylaxis".)

CYTOKINES AND CHEMOKINES — The mast cell is increasingly recognized as a source of multifunctional cytokines that may participate in the recruitment and activation of other cells in the inflammatory microenvironment [119]. Mast cells with different secretory granule protease phenotypes exhibit differences in their cytokine profiles, thereby indicating further heterogeneity depending on tissue localization [120].

The mast cell is a source of T helper type 2 (Th2) cytokines, which are believed important in the perpetuation of the allergic response. Both human MCT (mast cells containing tryptase) and MCTC (mast cell containing tryptase and chymase) demonstrate transcripts and immunoreactive protein for interleukin 4 (IL-4) in situ [120,121], and cultured human lung mast cells release IL-4 after activation with immunoglobulin E (IgE) and antigen [122].

Interleukin-4 — Interleukin 4 (IL-4) is implicated in the development and upregulation of Th2 cells, is required for the biosynthesis of IgE, and stimulates the production of cysteinyl leukotrienes in a positive feedback loop that results in reactive mast cell hyperplasia [105].

Interleukin-5 — Human lung mast cells release interleukin 5 (IL-5) when activated ex vivo through the high affinity IgE receptor, Fc-epsilon-RI. IL-5 is a potent eosinophil maturation and cytoprotective factor [123]. Cultured human bone marrow-derived mast cells release Granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation through Fc-epsilon-RI [124].

Interleukin-9 — Interleukin 9 (IL-9), originally identified as a T cell and mast cell growth factor, is produced concomitantly with other Th2 cytokines by CD4+Th2 cells [125]. IL-9 producing mast cells are recruited to the intestine in an experimental model of food allergy [126]. IL-9 and mast cell transcripts are increased in the intestine of atopic patients with food allergy [126].

Interleukin-33 — Interleukin-33 is an alarmin that is implicated in several disorders, including atopic diseases. There is some evidence that blocking IL-33 improves skin inflammation in atopic dermatitis [127].

TNF-alpha — Tumor necrosis factor-alpha (TNF-alpha, cachexin) was the first cytokine localized in human mast cells [128]. Some TNF-alpha may be constitutively stored in the granule, but the vast majority is induced with immunologic activation [129]. Studies using mast cell-deficient mice have demonstrated the importance of the mast cell-derived TNF-alpha in neutrophil recruitment in bacterial peritonitis, in protection from endotoxic shock, and in driving the initial immune response by directing antigen-presenting cell (dendritic cell) migration to local draining lymph nodes [130-132]. Mast cell-derived TNF-alpha also upregulates expression of endothelial adhesion molecules, such as endothelial-leukocyte adhesion molecule-1 (ELAM-1) and ICAM-1, facilitating adhesion and ingress of eosinophils and T cells to the inflammatory locus [133,134]. TNF-alpha derived from mast cells also may underlie lymph node hypertrophy in response to bacterial inflammation [135].

TGF-beta — Transcripts for transforming growth factor-beta (TGF-beta), a potent fibroblast activator and proliferation factor, are localized in human mast cells from fibrotic lung and rheumatoid synovium [136].

Chemokines — Mast cells release a number of chemokines, including the CC chemokine macrophage chemotactic protein-1 (MCP-1 or CCL2) and the CXC chemokine interleukin 8 (IL-8), which promotes neutrophil chemotaxis [137-139]. Transcripts for interleukin 1b (IL-1b), interleukin-13 (IL-3), and platelet-derived growth factor (PDGF) can be induced in the human mast cell line 1 (HMC-1), and studies in the mouse have implicated mast cell-derived IL-1 as critical to inflammatory joint disease [140,141].

SUMMARY

Types of mast cell mediators – Mast cells release a wide variety of mediators upon activation. These mediators can be divided into three overlapping categories: preformed mediators, newly synthesized lipid mediators, and cytokines and chemokines. (See 'Introduction' above.)

Preformed mediators – Preformed mediators are stored in secretory granules and released into the extracellular environment within seconds to minutes after mast cell activation. They are responsible for many of the acute signs and symptoms of mast cell-mediated allergic reactions. These mediators include histamine, neutral proteases, heparin proteoglycans, and some cytokines, such as tumor necrosis factor-alpha (TNF-alpha). (See 'Preformed mediators' above.)

Mediators formed upon activation – Following activation, mast cells use membrane phospholipids to synthesize additional eicosanoid mediators: Prostaglandins (PG), leukotrienes (LT), and platelet-activating factor (PAF). These mediators appear from 15 minutes to several hours after activation. Eicosanoids cause some of the symptoms of allergic reactions and are also important in cell recruitment and antigen presentation. (See 'Newly synthesized lipid mediators' above.)

Cytokines and chemokines – Mast cells produce multifunctional cytokines and chemokines that recruit and activate other cells to the inflammatory microenvironment. These include the T helper type 2 (Th2) cytokines, interleukin 4 (IL-4) and interleukin 5 (IL-5), which are thought to be important in the perpetuation of the allergic response, and several chemokines that recruit neutrophils and activate fibroblasts. (See 'Cytokines and chemokines' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges E Richard Stiehm, MD, who contributed as a Section Editor to an earlier version of this topic review.

The UpToDate editorial staff acknowledges Michael Gurish, PhD, now deceased, who contributed to an earlier version of this topic review.

  1. Xu X, Zhang D, Zhang H, et al. Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. J Exp Med 2006; 203:2907.
  2. Dvorak AM, Costa JJ, Morgan ES, et al. Diamine oxidase-gold ultrastructural localization of histamine in human skin biopsies containing mast cells stimulated to degranulate in vivo by exposure to recombinant human stem cell factor. Blood 1997; 90:2893.
  3. Schwartz LB, Irani AM, Roller K, et al. Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol 1987; 138:2611.
  4. Lowman MA, Rees PH, Benyon RC, Church MK. Human mast cell heterogeneity: histamine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-dependent and nonimmunologic stimuli. J Allergy Clin Immunol 1988; 81:590.
  5. Marshall JS, Jawdat DM. Mast cells in innate immunity. J Allergy Clin Immunol 2004; 114:21.
  6. Bryce PJ, Mathias CB, Harrison KL, et al. The H1 histamine receptor regulates allergic lung responses. J Clin Invest 2006; 116:1624.
  7. Leino L, Lilius EM. Histamine receptors on leukocytes are expressed differently in vitro and ex vivo. Int Arch Allergy Appl Immunol 1990; 91:30.
  8. Falus A, Merétey K. Histamine: an early messenger in inflammatory and immune reactions. Immunol Today 1992; 13:154.
  9. Arrang JM, Devaux B, Chodkiewicz JP, Schwartz JC. H3-receptors control histamine release in human brain. J Neurochem 1988; 51:105.
  10. Varty LM, Gustafson E, Laverty M, Hey JA. Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic vasoconstriction. Eur J Pharmacol 2004; 484:83.
  11. Morse KL, Behan J, Laz TM, et al. Cloning and characterization of a novel human histamine receptor. J Pharmacol Exp Ther 2001; 296:1058.
  12. Holm J, Hansen SI. Ligand binding characteristics and aggregation behavior of purified cow's milk folate binding protein depends on the presence of amphiphatic substances including cholesterol, phospholipids, and synthetic detergents. Biosci Rep 2002; 22:431.
  13. Dunford PJ, O'Donnell N, Riley JP, et al. The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. J Immunol 2006; 176:7062.
  14. Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther 2003; 305:1212.
  15. Ling P, Ngo K, Nguyen S, et al. Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 2004; 142:161.
  16. Moskovskiĭ AV. [Human tooth development in antenatal period (a luminescent-histochemical study)]. Morfologiia 2005; 128:45.
  17. Kushnir-Sukhov NM, Brown JM, Wu Y, et al. Human mast cells are capable of serotonin synthesis and release. J Allergy Clin Immunol 2007; 119:498.
  18. Avraham S, Austen KF, Nicodemus CF, et al. Cloning and characterization of the mouse gene that encodes the peptide core of secretory granule proteoglycans and expression of this gene in transfected rat-1 fibroblasts. J Biol Chem 1989; 264:16719.
  19. Stevens RL, Fox CC, Lichtenstein LM, Austen KF. Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells. Proc Natl Acad Sci U S A 1988; 85:2284.
  20. Pejler G, Rönnberg E, Waern I, Wernersson S. Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 2010; 115:4981.
  21. Schwartz LB, Riedel C, Caulfield JP, et al. Cell association of complexes of chymase, heparin proteoglycan, and protein after degranulation by rat mast cells. J Immunol 1981; 126:2071.
  22. Goldstein SM, Leong J, Schwartz LB, Cooke D. Protease composition of exocytosed human skin mast cell protease-proteoglycan complexes. Tryptase resides in a complex distinct from chymase and carboxypeptidase. J Immunol 1992; 148:2475.
  23. Ghildyal N, Friend DS, Stevens RL, et al. Fate of two mast cell tryptases in V3 mastocytosis and normal BALB/c mice undergoing passive systemic anaphylaxis: prolonged retention of exocytosed mMCP-6 in connective tissues, and rapid accumulation of enzymatically active mMCP-7 in the blood. J Exp Med 1996; 184:1061.
  24. Oscarsson LG, Pejler G, Lindahl U. Location of the antithrombin-binding sequence in the heparin chain. J Biol Chem 1989; 264:296.
  25. Weiler JM, Yurt RW, Fearon DT, Austen KF. Modulation of the formation of the amplification convertase of complement, C3b, Bb, by native and commercial heparin. J Exp Med 1978; 147:409.
  26. Gospodarowicz D, Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol 1986; 128:475.
  27. Murakami M, Nakatani Y, Kudo I. Type II secretory phospholipase A2 associated with cell surfaces via C-terminal heparin-binding lysine residues augments stimulus-initiated delayed prostaglandin generation. J Biol Chem 1996; 271:30041.
  28. Bingham CO 3rd, Murakami M, Fujishima H, et al. A heparin-sensitive phospholipase A2 and prostaglandin endoperoxide synthase-2 are functionally linked in the delayed phase of prostaglandin D2 generation in mouse bone marrow-derived mast cells. J Biol Chem 1996; 271:25936.
  29. Pejler G, Sadler JE. Mechanism by which heparin proteoglycan modulates mast cell chymase activity. Biochemistry 1999; 38:12187.
  30. Thompson HL, Schulman ES, Metcalfe DD. Identification of chondroitin sulfate E in human lung mast cells. J Immunol 1988; 140:2708.
  31. Irani AA, Schechter NM, Craig SS, et al. Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci U S A 1986; 83:4464.
  32. Schwartz LB. Effector cells of anaphylaxis: mast cells and basophils. Novartis Found Symp 2004; 257:65.
  33. Castells MC, Irani AM, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol 1987; 138:2184.
  34. Schwartz LB, Yunginger JW, Miller J, et al. Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest 1989; 83:1551.
  35. Caughey GH. Tryptase genetics and anaphylaxis. J Allergy Clin Immunol 2006; 117:1411.
  36. Maun HR, Jackman JK, Choy DF, et al. An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma. Cell 2019; 179:417.
  37. HOPSU VK, GLENNER GG. A histochemical enzyme kinetic system applied to the trypsin-like amidase and esterase activity in human mast cells. J Cell Biol 1963; 17:503.
  38. Schwartz LB, Lewis RA, Austen KF. Tryptase from human pulmonary mast cells. Purification and characterization. J Biol Chem 1981; 256:11939.
  39. Schwartz LB, Bradford TR, Littman BH, Wintroub BU. The fibrinogenolytic activity of purified tryptase from human lung mast cells. J Immunol 1985; 135:2762.
  40. Prieto-García A, Castells MC, Hansbro PM, Stevens RL. Mast cell-restricted tetramer-forming tryptases and their beneficial roles in hemostasis and blood coagulation. Immunol Allergy Clin North Am 2014; 34:263.
  41. Gruber BL, Marchese MJ, Suzuki K, et al. Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation. J Clin Invest 1989; 84:1657.
  42. Tam EK, Caughey GH. Degradation of airway neuropeptides by human lung tryptase. Am J Respir Cell Mol Biol 1990; 3:27.
  43. Caughey GH. Roles of mast cell tryptase and chymase in airway function. Am J Physiol 1989; 257:L39.
  44. Gruber BL, Kew RR, Jelaska A, et al. Human mast cells activate fibroblasts: tryptase is a fibrogenic factor stimulating collagen messenger ribonucleic acid synthesis and fibroblast chemotaxis. J Immunol 1997; 158:2310.
  45. Ruoss SJ, Hartmann T, Caughey GH. Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Invest 1991; 88:493.
  46. Walls AF, He S, Teran LM, et al. Granulocyte recruitment by human mast cell tryptase. Int Arch Allergy Immunol 1995; 107:372.
  47. Cairns JA, Walls AF. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J Immunol 1996; 156:275.
  48. Ui H, Andoh T, Lee JB, et al. Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. Eur J Pharmacol 2006; 530:172.
  49. Dwyer DF, Ordovas-Montanes J, Allon SJ, et al. Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation. Sci Immunol 2021; 6.
  50. Irani AM, Craig SS, DeBlois G, et al. Deficiency of the tryptase-positive, chymase-negative mast cell type in gastrointestinal mucosa of patients with defective T lymphocyte function. J Immunol 1987; 138:4381.
  51. Balzar S, Chu HW, Strand M, Wenzel S. Relationship of small airway chymase-positive mast cells and lung function in severe asthma. Am J Respir Crit Care Med 2005; 171:431.
  52. Balzar S, Fajt ML, Comhair SA, et al. Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program. Am J Respir Crit Care Med 2011; 183:299.
  53. Dougherty RH, Sidhu SS, Raman K, et al. Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma. J Allergy Clin Immunol 2010; 125:1046.
  54. Abonia JP, Blanchard C, Butz BB, et al. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol 2010; 126:140.
  55. Weidner N, Austen KF. Heterogeneity of mast cells at multiple body sites. Fluorescent determination of avidin binding and immunofluorescent determination of chymase, tryptase, and carboxypeptidase content. Pathol Res Pract 1993; 189:156.
  56. Irani AM, Goldstein SM, Wintroub BU, et al. Human mast cell carboxypeptidase. Selective localization to MCTC cells. J Immunol 1991; 147:247.
  57. Reynolds DS, Gurley DS, Austen KF. Cloning and characterization of the novel gene for mast cell carboxypeptidase A. J Clin Invest 1992; 89:273.
  58. Goldstein SM, Kaempfer CE, Proud D, et al. Detection and partial characterization of a human mast cell carboxypeptidase. J Immunol 1987; 139:2724.
  59. Goldstein SM, Kaempfer CE, Kealey JT, Wintroub BU. Human mast cell carboxypeptidase. Purification and characterization. J Clin Invest 1989; 83:1630.
  60. Goldstein SM, Leong J, Bunnett NW. Human mast cell proteases hydrolyze neurotensin, kinetensin and Leu5-enkephalin. Peptides 1991; 12:995.
  61. Metz M, Piliponsky AM, Chen CC, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science 2006; 313:526.
  62. Schneider LA, Schlenner SM, Feyerabend TB, et al. Molecular mechanism of mast cell mediated innate defense against endothelin and snake venom sarafotoxin. J Exp Med 2007; 204:2629.
  63. Schechter NM, Irani AM, Sprows JL, et al. Identification of a cathepsin G-like proteinase in the MCTC type of human mast cell. J Immunol 1990; 145:2652.
  64. Wintroub BU, Schechter NB, Lazarus GS, et al. Angiotensin I conversion by human and rat chymotryptic proteinases. J Invest Dermatol 1984; 83:336.
  65. Reilly CF, Schechter NB, Travis J. Inactivation of bradykinin and kallidin by cathepsin G and mast cell chymase. Biochem Biophys Res Commun 1985; 127:443.
  66. Caughey GH, Leidig F, Viro NF, Nadel JA. Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. J Pharmacol Exp Ther 1988; 244:133.
  67. Briggaman RA, Schechter NM, Fraki J, Lazarus GS. Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes. J Exp Med 1984; 160:1027.
  68. Mizutani H, Schechter N, Lazarus G, et al. Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase. J Exp Med 1991; 174:821.
  69. Sommerhoff CP, Caughey GH, Finkbeiner WE, et al. Mast cell chymase. A potent secretagogue for airway gland serous cells. J Immunol 1989; 142:2450.
  70. Mackins CJ, Kano S, Seyedi N, et al. Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. J Clin Invest 2006; 116:1063.
  71. Silver RB, Reid AC, Mackins CJ, et al. Mast cells: a unique source of renin. Proc Natl Acad Sci U S A 2004; 101:13607.
  72. Le TH, Coffman TM. A new cardiac MASTer switch for the renin-angiotensin system. J Clin Invest 2006; 116:866.
  73. Abonia JP, Friend DS, Austen WG Jr, et al. Mast cell protease 5 mediates ischemia-reperfusion injury of mouse skeletal muscle. J Immunol 2005; 174:7285.
  74. Boyce JA. Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunol Rev 2007; 217:168.
  75. Yokomizo T, Uozumi N, Takahashi T, et al. Leukotriene A4 hydrolase and leukotriene B4 metabolism. J Lipid Mediat Cell Signal 1995; 12:321.
  76. Church MK, el-Lati S, Caulfield JP. Neuropeptide-induced secretion from human skin mast cells. Int Arch Allergy Appl Immunol 1991; 94:310.
  77. el-Lati SG, Dahinden CA, Church MK. Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. J Invest Dermatol 1994; 102:803.
  78. Church MK, et al. Functional heterogeneity of human mast cells. In: Mast cell and basophil differentiation and function in health and disease, Galli SJ, Austen KF (Eds), Raven Press, New York 1989.
  79. Murray JJ, Tonnel AB, Brash AR, et al. Release of prostaglandin D2 into human airways during acute antigen challenge. N Engl J Med 1986; 315:800.
  80. Knani J, Campbell A, Enander I, et al. Indirect evidence of nasal inflammation assessed by titration of inflammatory mediators and enumeration of cells in nasal secretions of patients with chronic rhinitis. J Allergy Clin Immunol 1992; 90:880.
  81. O'Sullivan S, Dahlén B, Dahlén SE, Kumlin M. Increased urinary excretion of the prostaglandin D2 metabolite 9 alpha, 11 beta-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction. J Allergy Clin Immunol 1996; 98:421.
  82. Roberts LJ 2nd, Sweetman BJ, Lewis RA, et al. Increased production of prostaglandin D2 in patients with systemic mastocytosis. N Engl J Med 1980; 303:1400.
  83. Matsuoka T, Hirata M, Tanaka H, et al. Prostaglandin D2 as a mediator of allergic asthma. Science 2000; 287:2013.
  84. Metcalfe DD. The treatment of mastocytosis: an overview. J Invest Dermatol 1991; 96:55S.
  85. Flower RJ, Harvey EA, Kingston WP. Inflammatory effects of prostaglandin D2 in rat and human skin. Br J Pharmacol 1976; 56:229.
  86. Hardy CC, Robinson C, Tattersfield AE, Holgate ST. The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N Engl J Med 1984; 311:209.
  87. Pugliese G, Spokas EG, Marcinkiewicz E, Wong PY. Hepatic transformation of prostaglandin D2 to a new prostanoid, 9 alpha,11 beta-prostaglandin F2, that inhibits platelet aggregation and constricts blood vessels. J Biol Chem 1985; 260:14621.
  88. Goetzl EJ. Oxygenation products of arachidonic acid as mediators of hypersensitivity and inflammation. Med Clin North Am 1981; 65:809.
  89. Raible DG, Schulman ES, DiMuzio J, et al. Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils. J Immunol 1992; 148:3536.
  90. Urade Y, Hayaishi O. Prostaglandin D2 and sleep regulation. Biochim Biophys Acta 1999; 1436:606.
  91. Morrow JD, Awad JA, Oates JA, Roberts LJ 2nd. Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans. J Invest Dermatol 1992; 98:812.
  92. Lewis RA, Soter NA, Diamond PT, et al. Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE. J Immunol 1982; 129:1627.
  93. MacGlashan DW Jr, Schleimer RP, Peters SP, et al. Generation of leukotrienes by purified human lung mast cells. J Clin Invest 1982; 70:747.
  94. Tager AM, Bromley SK, Medoff BD, et al. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 2003; 4:982.
  95. Taube C, Miyahara N, Ott V, et al. The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness. J Immunol 2006; 176:3157.
  96. Lam BK, Xu K, Atkins MB, Austen KF. Leukotriene C4 uses a probenecid-sensitive export carrier that does not recognize leukotriene B4. Proc Natl Acad Sci U S A 1992; 89:11598.
  97. Bankova LG, Boyce JA. A new spin on mast cells and cysteinyl leukotrienes: Leukotriene E4 activates mast cells in vivo. J Allergy Clin Immunol 2018; 142:1056.
  98. Juhlin L, Hammarström S. Effects of intradermally injected leukotriene C4 and histamine in patients with urticaria, psoriasis and atopic dermatitis. Br J Dermatol 1982; 107 Suppl 23:106.
  99. Arm JP, Lee TH. Sulphidopeptide leukotrienes in asthma. Clin Sci (Lond) 1993; 84:501.
  100. Austen KF. The Paul Kallós Memorial Lecture. From slow-reacting substance of anaphylaxis to leukotriene C4 synthase. Int Arch Allergy Immunol 1995; 107:19.
  101. Miadonna A, Tedeschi A, Leggieri E, et al. Behavior and clinical relevance of histamine and leukotrienes C4 and B4 in grass pollen-induced rhinitis. Am Rev Respir Dis 1987; 136:357.
  102. Wenzel SE, Larsen GL, Johnston K, et al. Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. Am Rev Respir Dis 1990; 142:112.
  103. Taylor GW, Taylor I, Black P, et al. Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Lancet 1989; 1:584.
  104. Maltby NH, Ind PW, Causon RC, et al. Leukotriene E4 release in cold urticaria. Clin Exp Allergy 1989; 19:33.
  105. Jiang Y, Kanaoka Y, Feng C, et al. Cutting edge: Interleukin 4-dependent mast cell proliferation requires autocrine/intracrine cysteinyl leukotriene-induced signaling. J Immunol 2006; 177:2755.
  106. Jiang Y, Borrelli LA, Kanaoka Y, et al. CysLT2 receptors interact with CysLT1 receptors and down-modulate cysteinyl leukotriene dependent mitogenic responses of mast cells. Blood 2007; 110:3263.
  107. Paruchuri S, Jiang Y, Feng C, et al. Leukotriene E4 activates peroxisome proliferator-activated receptor gamma and induces prostaglandin D2 generation by human mast cells. J Biol Chem 2008; 283:16477.
  108. Triggiani M, Hubbard WC, Chilton FH. Synthesis of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine by an enriched preparation of the human lung mast cell. J Immunol 1990; 144:4773.
  109. Imaizumi TA, Stafforini DM, Yamada Y, et al. Platelet-activating factor: a mediator for clinicians. J Intern Med 1995; 238:5.
  110. Okada S, Kita H, George TJ, et al. Transmigration of eosinophils through basement membrane components in vitro: synergistic effects of platelet-activating factor and eosinophil-active cytokines. Am J Respir Cell Mol Biol 1997; 16:455.
  111. Prpic V, Uhing RJ, Weiel JE, et al. Biochemical and functional responses stimulated by platelet-activating factor in murine peritoneal macrophages. J Cell Biol 1988; 107:363.
  112. Czarnetzki B. Increased monocyte chemotaxis towards leukotriene B4 and platelet activating factor in patients with inflammatory dermatoses. Clin Exp Immunol 1983; 54:486.
  113. Thivierge M, Rola-Pleszczynski M. Platelet-activating factor enhances interleukin-6 production by alveolar macrophages. J Allergy Clin Immunol 1992; 90:796.
  114. Smith LJ. The role of platelet-activating factor in asthma. Am Rev Respir Dis 1991; 143:S100.
  115. Zimmerman GA, McIntyre TM, Prescott SM. Adhesion and signaling in vascular cell--cell interactions. J Clin Invest 1996; 98:1699.
  116. Stafforini DM, Satoh K, Atkinson DL, et al. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase. J Clin Invest 1996; 97:2784.
  117. Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med 2008; 358:28.
  118. Hozawa S, Haruta Y, Ishioka S, Yamakido M. Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma. Am J Respir Crit Care Med 1995; 152:1198.
  119. Gordon JR, Burd PR, Galli SJ. Mast cells as a source of multifunctional cytokines. Immunol Today 1990; 11:458.
  120. Bradding P, Okayama Y, Howarth PH, et al. Heterogeneity of human mast cells based on cytokine content. J Immunol 1995; 155:297.
  121. Bradding P, Feather IH, Wilson S, et al. Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. J Immunol 1993; 151:3853.
  122. Bradding P, Feather IH, Howarth PH, et al. Interleukin 4 is localized to and released by human mast cells. J Exp Med 1992; 176:1381.
  123. Jaffe JS, Glaum MC, Raible DG, et al. Human lung mast cell IL-5 gene and protein expression: temporal analysis of upregulation following IgE-mediated activation. Am J Respir Cell Mol Biol 1995; 13:665.
  124. Bressler RB, Lesko J, Jones ML, et al. Production of IL-5 and granulocyte-macrophage colony-stimulating factor by naive human mast cells activated by high-affinity IgE receptor ligation. J Allergy Clin Immunol 1997; 99:508.
  125. Shik D, Tomar S, Lee JB, et al. IL-9-producing cells in the development of IgE-mediated food allergy. Semin Immunopathol 2017; 39:69.
  126. Chen CY, Lee JB, Liu B, et al. Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy. Immunity 2015; 43:788.
  127. Chen YL, Gutowska-Owsiak D, Hardman CS, et al. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci Transl Med 2019; 11.
  128. Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature 1990; 346:274.
  129. Gordon JR, Galli SJ. Release of both preformed and newly synthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE-dependent biological responses. J Exp Med 1991; 174:103.
  130. Echtenacher B, Männel DN, Hültner L. Critical protective role of mast cells in a model of acute septic peritonitis. Nature 1996; 381:75.
  131. Malaviya R, Ikeda T, Ross E, Abraham SN. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 1996; 381:77.
  132. Suto H, Nakae S, Kakurai M, et al. Mast cell-associated TNF promotes dendritic cell migration. J Immunol 2006; 176:4102.
  133. Klein LM, Lavker RM, Matis WL, Murphy GF. Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion. Proc Natl Acad Sci U S A 1989; 86:8972.
  134. Wegner CD, Gundel RH, Reilly P, et al. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science 1990; 247:456.
  135. McLachlan JB, Hart JP, Pizzo SV, et al. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nat Immunol 2003; 4:1199.
  136. Qu Z, Liebler JM, Powers MR, et al. Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am J Pathol 1995; 147:564.
  137. Alam R. Chemokines in allergic inflammation. J Allergy Clin Immunol 1997; 99:273.
  138. Möller A, Lippert U, Lessmann D, et al. Human mast cells produce IL-8. J Immunol 1993; 151:3261.
  139. Gurish MF, Boyce JA. Mast cells: ontogeny, homing, and recruitment of a unique innate effector cell. J Allergy Clin Immunol 2006; 117:1285.
  140. Nilsson G, Svensson V, Nilsson K. Constitutive and inducible cytokine mRNA expression in the human mast cell line HMC-1. Scand J Immunol 1995; 42:76.
  141. Nigrovic PA, Binstadt BA, Monach PA, et al. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A 2007; 104:2325.
Topic 3972 Version 17.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟