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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of mediator release from mast cells and basophils by diisopropylfluorophosphate (DFP) and other organophosphorus compounds known to inhibit serine esterases has in the past led to the hypothesis that immunologic triggering of these cells involves an activatable serine esterase. In this study we have shown that two nonphosphorylating or poorly phosphorylating structural analogs of two potent phosphorylators inhibit release of incorporated serotonin from cultured rat basophil leukemia cells. We conclude that, by itself, inhibition of immunologic mast cell triggering by phosphorylating organophosphorus compounds can no longer be considered evidence for involvement of an activatable serine esterase in mast cell triggering.
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PMID:IgE mediated triggering of rat basophil leukemia cells: lack of evidence for serine esterase activation. 44 21

Ovine mast cells generated in vitro from bone marrow (BMMC) were compared with mucosal mast cells (MMC) isolated from parasitised abomasum. Ultrastructurally, the granules of BMMC were partially developed and immature. Both cells types contained beta-hexosaminidase, arylsulfatase, histamine, dopamine and sheep mast cell proteinase (SMCP). Greater amounts of beta-hexosaminidase, but less SMCP, histamine and arylsulfatase were present in BMMC. Stimulation with calcium ionophore A23187 caused the secretion of granule constituents and generation of leukotriene C4 by BMMC in a dose-dependent manner. An additional [3H]diisopropylfluorophosphate-binding 31,500 mol. wt. serine esterase, antigenically related to SMCP (27,000 mol. wt.) was present in cultures of BMMC but was not detected in isolated MMC. Both enzymes were detected in BMMC by Day 7 of culture and were secreted concomitantly following stimulation of BMMC with ionophore.
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PMID:Characterisation of ovine mast cells derived from in vitro culture of haemopoietic tissue. 153 49

The interaction of mouse intestinal mast cell proteinase (IMCP) with serine proteinase inhibitors (serpins) in blood was analysed: (i) by examining the capacity of the inhibitors in blood to block the binding of the irreversible serine esterase inhibitor [3H]diisopropyl fluorophosphate (DFP); (ii) by Western blotting. The binding of [3H]DFP to IMCP was blocked very rapidly by inhibitors in mouse serum and, by Western blotting, this inhibition was associated with the appearance of a 73,000 MW proteinase/inhibitor complex together with a series of higher (greater than 100,000) MW complexes. IMCP was not dissociated from these complexes when electrophoresed under reducing conditions, although prior heat treatment of mouse serum (60 for 30-160 min) abolished the formation of all proteinase/inhibitor complexes. Similarly, the activity of a 48,000 MW inhibitor of chymotrypsin was abolished by heat treatment. A titration experiment established that between 0.5 and 5 mg IMCP were inhibited per ml of serum. The properties and MW of the IMCP inhibitor complexes are typical of serpins and suggest that IMCP secreted during intestinal immunological reactions would be rapidly and irreversibly inactivated by plasma-derived inhibitors.
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PMID:Interaction of murine intestinal mast cell proteinase with inhibitors (serpins) in blood; analysis by SDS-PAGE and western blotting. 231 50

The appearance in blood of rat mast cell protease II (RMCPII) and glycosaminoglycan (GAG) was examined in normal and Nippostrongylus brasiliensis-primed rats challenged intravenously with worm antigen. Systemic release of these two products occurred only in immune recipients of antigen; substantial levels of RMCPII were also present in the intestinal perfusates of these same rats and there was depletion of both RMCPII and mucosal mast cells (MMC) from the intestinal mucosa. Depletion of MMC was evident after staining for proteoglycan or for serine esterase and the mast cell counts with both histochemical techniques were highly correlated. Taken together, the results suggest that MMC are likely to be the principal source of secreted GAG and RMCPII.
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PMID:The presence in blood of both glycosaminoglycan and mucosal mast cell protease following systemic anaphylaxis in the rat. 388 73

This review details the biochemical events that follow IgE dimerization by antigen and cross-linking of receptors and are linked with the early rise in cyclic AMP. That the monophasic rise in cyclic AMP at 15 s is essential to the degranulation process is evident by pharmacological manipulation of adenylate cyclase, using specific activators and inhibitors to achieve potentiation and inhibition of immunologic release, respectively. Although only a small percentage of membrane adenylate cyclase is transmembrane linked to IgE-Fc perturbation, its product, cyclic AMP, is elevated during activation and is responsible for the activation of two protein kinase isoenzymes at 30-60 s. This sequence appears to be essential for secretion to occur, as evidenced by dose-related inhibition of both beta-hexosaminidase release and protein kinase activation by adenylate cyclase inhibitors. Competitive activation of cyclic AMP-dependent protein kinase activity by a phosphodiesterase inhibitor leads to inhibition of mediator release by diverting an essential enzyme or recruiting an inhibitory sequence. The precise functional role of the mast cell cyclic AMP-dependent protein kinases has not yet been identified, but there is much evidence in other cell types that protein phosphorylation is an essential accompaniment to cellular regulation. Although other apparently essential biochemical steps are noted, such as uncovering a serine esterase, methylation of membrane phospholipid, and increased Ca2+ influx, only a portion of the activation-secretion response is presented here as a sequence, namely, the IgE-Fc receptor-initiated, transmembrane-coupled activation of adenylate cyclase and the subsequent cytoplasmic cyclic AMP-dependent activation of types I and II protein kinases.
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PMID:Enzymatic regulation of mast cell activation and secretion by adenylate cyclase and cyclic AMP-dependent protein kinases. 617 64

To examine the putative role of an endogenous serine esterase in mast cell activation, we have investigated the effect of inhibitors of, and substrates for, alpha-chymotrypsin in normal and permeabilized rat mast cells. These agents effectively blocked histamine release induced by anti-IgE, with an enhanced potency in permeabilized cells, but were ineffective against secretion evoked by compound 48/80. Activation of a chymotryptic enzyme, as evidenced by hydrolysis of a fluorescent substrate, was directly demonstrated following immunologic stimulation of permeabilized mast cells. No such activation was observed with compound 48/80. Immunologic stimulation also led to a significant increase in the total chymotryptic activity recoverable from the cells.
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PMID:Involvement of a serine protease in mast cell activation. 752 53

Interleukin 9 (IL-9) is a TH2 cytokine that has been shown to promote the antigen-independent growth of some mouse T helper clones. To characterize the specificity of IL-9-mediated T cell activation, we used a murine T cell clone that could grow with either IL-9 or IL-2. After differential hybridization of a cDNA library, we isolated three genes that were expressed preferentially in the presence of IL-9. Two of them correspond respectively to granzyme A and granzyme B, two proteases expressed by activated T cells. By Northern blot hybridization and functional assays, we found that IL-9 induced the expression of granzyme B in several T cell clones as well as in mast cell lines. In addition, other proteases such as the mouse mast cell proteases were also found to be expressed by IL-9-activated T cell clones. The third IL-9-induced cDNA corresponds to the alpha-chain of the high-affinity receptor for IgE. Several T cell clones expressed this IgE receptor mRNA and were able to bind IgE with high affinity. Taken together, our results indicate that IL-9 induces a mast cell-like phenotype in T cell clones.
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PMID:IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones. 773 Jun 12

Genes encoding T-cell-receptor alpha/delta chains, neutrophil cathepsin G, and lymphocyte CGL/granzymes are closely linked on chromosomal band 14q11.2. The current work identifies the human mast cell chymase gene (CMA1) as the fourth protease in this cluster and maps the gene to within 150 kb of the cathepsin G gene. The gene order is centromere-T cell receptor alpha/delta-CGL-1/granzyme B-CGL-2/granzyme H-cathepsin G-chymase. Chymase and cathepsin G genes are shown to be cotranscribed in the human mast cell line HMC-1 and in U-937 cells. Other cells transcribe cathepsin G or CGL/granzyme genes, but not chymase genes, suggesting a capacity for independent regulation. Comparison of the 5' flank of the chymase gene with those of cathepsin G and CGL/granzymes reveals little overall homology. Only short regions of the 5' flanks of the human and murine chymase gene sequenced to date are similar, suggesting that they are more distantly related than human and rodent CGL-1/granzyme B, the flanks of which are highly homologous. The expression patterns and clustering of genes provide possible clues to the presence of locus control regions that orchestrate lineage-restricted expression of leukocyte and mast cell proteases.
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PMID:The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression. 846 56

We have examined the effect of alpha-chymotrypsin on isolated mast cells from different sources. The enzyme induced a dose-dependent secretion of histamine from purified and non-purified populations of rat peritoneal mast cells. The release was non-cytotoxic and was inhibited by metabolic blockers and extremes of temperature. The process was relatively slow, being essentially complete within 20 min, and was unaffected by phosphatidylserine. A substantial component of the secretion persisted in the absence of extracellular Ca2+. The release was suppressed by extremes of pH and a variety of anti-allergic compounds and serine esterase inhibitors. In addition to the secretion of preformed mediators, alpha-chymotrypsin also induced the metabolism of arachidonic acid, resulting in the release of prostaglandin D2 in a dose-related manner from purified rat peritoneal mast cells. alpha-Chymotrypsin exhibited a marked tissue and species selectivity in its action and tissue mast cells of the rat, guinea pig and human were generally resistant to the enzyme except at cytotoxic concentrations. On the basis of these results, the possible role of endogenous serine esterases in mast cell activation is discussed.
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PMID:Some studies on the effects of alpha-chymotrypsin on mast cells from the rat and other species. 872 May 91

Using a recently developed PCR-based strategy, a cDNA encoding a novel mouse mast cell (MC) serine protease (MMCP-8) was isolated and characterized. The MMCP-8 mRNA contains an open reading frame of 247 amino acids (aa), divided into a signal sequence of 18 aa followed by a 2-aa activation peptide (Gly-Glu) and a mature protease of 227 aa. The mature protease has an M(r) of 25072, excluding post-translational modifications, a net positive charge of +12 and six potential N-glycosylation sites. MMCP-8 showed a high degree of homology with mouse granzyme B in the critical regions for determining substrate cleavage specificity, indicating that MMCP-8, similar to granzyme B, preferentially cleaves after Asp residues. A comparative analysis of the aa sequence of MMCP-8 with other hematopoietic serine proteases shows that it is more closely related to cathepsin G and T cell granzymes than to the MC chymases. We therefore conclude that MMCP-8 belongs to a novel subfamily of mouse MC proteases distinct from both the classical chymases and tryptases. Southern blot analysis of BALB/c genomic DNA indicated that only one MMCP-8 gene (or MMCP-8 like gene) is present in the mouse genome. Northern blot analysis of rodent hematopoietic cell lines revealed high levels of MMCP-8 mRNA in a mouse connective tissue MC-like tumor line. However, MMCP-8 mRNA could not be detected in mouse liver, intestine, lung or ears, indicating very low expression in normal tissues. Analysis of the expression of different MMCP in the tissues of Schistosoma mansoni-infected BALB/c mice showed a strong increase in MMCP-8 levels in the lungs but not in the intestines of infected animals, suggesting the presence of a novel subpopulation of MC in the lungs that expressed MMCP-8, either alone or in combination with MMCP-5 and carboxypeptidase A. The dramatic increase in MMCP-1 and MMCP-2 levels but not of MMCP-8 in the intestines of parasitized animals also shows that MMCP-8 is not expressed in mucosal MC in the mouse. This latter is in clear contrast to what has been observed in the rat where the MMCP-8 homologues, RMCP-8, -9 and -10, can be considered as true mucosal MC proteases.
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PMID:Characterization of mouse mast cell protease-8, the first member of a novel subfamily of mouse mast cell serine proteases, distinct from both the classical chymases and tryptases. 954 98


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