Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of transglutaminase in the growth-factor-dependent mouse mast cell line PT18 was accomplished through its characteristic catalytic properties (specificity, calcium dependency, and inhibition by iodoacetamide); and by both immunoprecipitation and Western blot analysis using affinity purified antibody. The enzymatic activity in these cells increased in association with the release of histamine from the cells induced by an IgE-dependent mechanism or by exposure to the ionophores A23187 or Br-x537A. The increase in transglutaminase activity was paralleled by a marked increase in the level of protein-bound gamma-glutamylhistamine, determined in radiolabeled form in mast cells that were either metabolically labeled with [3H]histidine or incubated with [3H]histamine before degranulation. The highest level of bound gamma-glutamylhistamine was found in the immunologically stimulated cells. Enzymatic activity and the gamma-glutamyl derivative were associated primarily with the cells, both before and after stimulation. Separation of gamma-glutamylhistamine in a proteolytic digest of these cells was carried out using a combination of ion exchange chromatography and high performance liquid chromatography. The gamma-glutamyl compound was identified and quantitated through the enzymatic production of histamine with the use of gamma-glutamylamine cyclotransferase, an enzyme specific for the disassembly of gamma-glutamylamines.
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PMID:Activation of transglutaminase and production of protein-bound gamma-glutamylhistamine in stimulated mouse mast cells. 241 84

Acid hydrolysis of trichloroacetic acid precipitate from rat tissue (liver, kidney and testis) homogenate released significant amounts of acid-insoluble putrescine, spermidine and spermine. Following incubation of liver homogenate with [1,4-14C]putrescine, 1.4% of total radioactivity and 1.0% of labelled diamine were recovered in the acid-insoluble fraction. Exhaustive digestion of acid-precipitable material with proteinases (Pronase, aminopeptidase M, carboxypeptidase A, B and Y) revealed the presence of di- and polyamines and of N1-(gamma-glutamyl)spermidine, N1-(gamma-glutamyl)spermine and N1,N12-bis(gamma-glutamyl)spermine. These derivatives were identified both by chromatographic analysis and by enzymatic digestion with purified gamma-glutamylamine cyclotransferase. The finding of di- and polyamine gamma-glutamyl derivatives in the proteinase-digested acid-insoluble fraction of homogenate may be considered as a proof of the in vivo transglutaminase-catalyzed binding of polyamines to proteins. This evidence suggests that di- and polyamines might have an important role in mammalian tissues through covalent binding to proteins by either one or both the primary amino groups.
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PMID:Presence of di- and polyamines covalently bound to protein in rat liver. 286 56

Physiologic and pathologic events associated with cutaneous differentiation and repair are the result of a concerted action of various types of resident tissue cells. In vitro models simulating this complex in vivo situation are therefore needed to clarify the specific contribution and relevant interaction of, for example, dermal mast cells with other major cutaneous cells. The aim of this study was to establish a long-term coculture model that includes dermal mast cells, dermal fibroblasts, and keratinocytes in a human skin equivalent organotypic setting. Normal dermal mast cells and fibroblasts (1:4) were enclosed in collagen gel and normal keratinocytes were grown on top with exposure to the air interface. Under these conditions, mast cell integrity and functionality was preserved even after 4 wk of culture, as shown by electron microscopy and immunohistochemistry using antibodies against the mast-cell-specific granule enzyme tryptase and the receptors for stem cell factor and IgE. Mast cells also released histamine on stimulation with anti-IgE, and on ultrastructure were found to degranulate, with decrease of granule matrix density and formation of cell-cell contacts with fibroblasts. After 2 wk of culture, keratinocytes had formed an epidermis-like multilayer and were able to proliferate and differentiate, as shown by bromodeoxyuridine incorporation of basal cells and immunohistochemical staining for transglutaminase and cytokeratins 1 and 10. The model presented here thus provides a potentially relevant tool to further clarify the interaction of dermal mast cells with major other skin cells and their contribution to cutaneous physiology, repair processes, and pathology.
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PMID:A long-term coculture model for the study of mast cell-keratinocyte interactions. 1219 Aug 64

The skin is a common target of cellular and/or antibody mediated pathological immune responses. Pemphigoids, pemphigus vulgaris and dermatitis herpetiformis are bullous disease due to autoantibodies targeting specific proteins of the skin. The pemphigoid autoantigens are the BP180 and the BP230 antigens, two components of the epithelial basement membrane zone. Additional antigenic targets reported in a portion of patients are laminin 5, the alpha6 subunit of the hemidesmosomal integrin alpha6beta4 and a glycoprotein termed p200. The epidermal and mucosal epithelial cells detachment (acantholysis) characteristic of pemphigus vulgaris is induced by autoantibodies directed against the desmoglein 3 and 1. The desmogleins are desmosomal cadherins, which play a major role in the cell-to-cell adhesion. Dermatitis herpetiformis is regarded as cutaneous phenotype of coeliac disease. A novel autoimmune hypothesis of coeliac disease links wheat gliadin and tissue transglutaminase (TG2) in the gut, which leads to T cell response and IgA autoantibody formation. In dermatitis herpetiformis skin the target for IgA deposition seems to be epidermal TG3. Urticaria is a complex syndrome caused by both immune and non-immune mechanisms. In a subsets of patients with chronic urticaria mast cell degranulation is induced by autoantibodies directed against the a-subunit of the high-affinity IgE receptor, and/or the IgE.
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PMID:New insights into the autoantibody-mediated mechanisms of autoimmune bullous diseases and urticaria. 1646 21