Mast Cell Mediators in Allergic Inflammation and Mastocytosis
Section snippets
Histamine
Histamine is an amine produced by the decarboxylation of histidine, and it is stored in the secretory granules of all mature mast cells including connective tissues, mucosal membranes, skin and basophils [50], [51]. No differences are seen in the amounts of histamine stored in mast cells reflecting a similar mechanism for synthesis and storage [50], [51]. Once released into circulation, histamine is metabolized by histamine methyl transferase after one pass through the system. Plasma histamine
Membrane-derived lipid mediators
Human mast cells generate and release eicosanoid lipid mediators through a transmembrane activation signal with calcium influx [45], [90]. Prostaglandins and leukotrienes are metabolic products of AA derived from membrane phospholipids through the action of phospholipase enzymes (eg, PLA2) [91]. Other products of AA include hydroxyeicosatetraenoic acids (HETEs), lipoxins, epoxyeicosatrienoic acids, and isopropanes, which contribute to modulate inflammatory responses [92]. Cytosolic (type IV)
Chemokines and cytokines
Human mast cells are a source of multifunctional cytokines, but little is known of the regulation and secretion of cytokines and chemokines by patients with mastocytosis. [129]. Preformed TNFα, found in human skin and pulmonary mast cell granules, is released after IgE-, IgG-, and TLR-mediated activation. High-density oligonucleotide probe arrays (GeneChip analysis) have permitted elucidation of the cytokine gene expression pattern after mast cells have been activated through FcɛRI ligation and
Summary
Mast cells possess an array of potent inflammatory mediators capable of inducing acute symptoms after cell activation, including urticaria, angioedema, bronchoconstriction, diarrhea, vomiting, hypotension, cardiovascular collapse, and death in few minutes. In contrast, mast cells can provide an array of beneficial mediators in the setting of acute infections, cardiovascular diseases, and cancer. The balance between the detrimental and beneficial roles of mast cells is not completely understood.
References (178)
- et al.
Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases
Hepatology
(1995) - et al.
The presence of membrane-bound stem cell factor on highly immature nonmetachromatic mast cells in the peripheral blood of a patient with aggressive systemic mastocytosis
J Allergy Clin Immunol
(1996) - et al.
Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI-cell population
Blood
(1994) - et al.
Mast cell lineage development and phenotypic regulation
Leuk Res
(2001) - et al.
Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin
Blood
(1995) - et al.
The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus
Cell
(1990) - et al.
Quantitation of inflammatory cells in the nasal mucosa of patients with allergic rhinitis and normal subjects
J Allergy Clin Immunol
(1995) - et al.
A survey of the number and distribution of mast cells in the skin of patients with mast cell disorders
J Allergy Clin Immunol
(1988) - et al.
Tryptase levels in nasal-lavage fluid as an indicator of the immediate allergic response
J Allergy Clin Immunol
(1988) - et al.
Patterns of inflammatory responses following rechallenge of skin late-phase allergic reaction sites
J Allergy Clin Immunol
(1998)
FcepsilonRI signaling observed from the inside of the mast cell membrane
Mol Immunol
Intracellular degradation of Fc gamma RIII in mouse bone marrow culture-derived progenitor mast cells prevents its surface expression and associated function
J Biol Chem
Activation of human mast cells by aggregated IgG through FcgammaRI: additive effects of C3a
Clin Immunol
Acetylsalicylic acid-induced release of HSP70 from mast cells results in cell activation through TLR pathway
Exp Hematol
Complexes of heparin proteoglycans, chondroitin sulfate E proteoglycans, and [3H]diisopropyl fluorophosphate-binding proteins are exocytosed from activated mouse bone marrow-derived mast cells
J Biol Chem
The role of the mast cell in asthma: induction of airway hyperresponsiveness by interaction with smooth muscle?
J Allergy Clin Immunol
Analysis of plasma histamine levels in patients with mast cell disorders
Am J Med
The effect of H1 and H2 blockade on cutaneous histamine response in man
J Allergy Clin Immunol
Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat
Eur J Pharmacol
Improved diagnosis of mastocytosis by measurement of the major urinary metabolite of prostaglandin D2
J Invest Dermatol
Detection of the major urinary metabolite of prostaglandin D2 in the circulation: demonstration of elevated levels in patients with disorders of systemic mast cell activation
J Allergy Clin Immunol
Characterization of recombinant human chymase expressed in Escherichia coli
Jpn J Pharmacol
Isolation and molecular cloning of mast cell carboxypeptidase A. A novel member of the carboxypeptidase gene family
J Biol Chem
Human skin mast cell carboxypeptidase: functional characterization, cDNA cloning, and genealogy
J Invest Dermatol
Fibroblast growth factor-2
Int J Biochem Cell Biol
Internalization and degradation of type IIA phospholipase A(2) in mast cells
Biochem Biophys Res Commun
Prostaglandin endoperoxide synthase-1 and -2 couple to different transmembrane stimuli to generate prostaglandin D2 in mouse bone marrow-derived mast cells
J Biol Chem
The orientation of prostaglandin endoperoxide synthases-1 and -2 in the endoplasmic reticulum
J Biol Chem
Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells
J Immunol
Development of mast cells from grafted bone marrow cells in irradiated mice
Nature
Distribution of mast-cell precursors in hematopoietic and lymphopoietic tissues of mice
J Exp Med
Mast cells in human keloid, small intestine, and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase
Am J Pathol
Ultrastructural analysis of human T and TC mast cells identified by immunoelectron microscopy
Lab Invest
Ultrastructural analysis of maturing human T and TC mast cells in situ
Lab Invest
Pathology of the lymph node and spleen in systemic mast cell disease
Mod Pathol
Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies
J Histochem Cytochem
Characterization of histamine secretion from mechanically dispersed human lung mast cells: effects of anti-IgE, calcium ionophore A23187, compound 48/80, and basic polypeptides
J Immunol
Isolation and characterization of human intestinal mucosal mast cells
J Immunol
Mast cell biochemical and functional heterogeneity
Transplant Proc
Mast cells expressing chymase but not tryptase can be derived by culturing human progenitors in conditioned medium obtained from a human mastocytosis cell strain with c-kit ligand
J Immunol
Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor
Proc Natl Acad Sci USA
The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells
J Exp Med
Kit as a human oncogenic tyrosine kinase
Cell Mol Life Sci
Tyrosine kinase-deficient Wv c-kit induces mast cell adhesion and chemotaxis
Am J Physiol
Regulation of mast cell development
Chem Immunol Allergy
Comparison of airway immunopathology of eosinophilic bronchitis and asthma
Thorax
Mast cells: a cellular link between autoantibodies and inflammatory arthritis
Science
Persistent wheezing in very young children is associated with lower respiratory inflammation
Am J Respir Crit Care Med
Mast cell numbers and histamine levels in synovial fluids from patients with diverse arthritides
Arthritis Rheum
Critical protective role of mast cells in a model of acute septic peritonitis
Nature
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