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)

Padawer has proposed that rat mast cells in the peritoneal cavity have an extended lifespan and under normal conditions exhibit little turnover of their secretory granules. We have examined several constituents of the granules as part of a study of the structure and function of these organelles. The previously described increase in volume of mast cells with age of the rats from which the cells are obtained is associated with an increase in the quantity of histamine, heparin, beta-glucuronidase and mast cell protease. While the former 3 granule components increase in parallel with mast cell volume, the increase in protease between 3- and 6-month-old rats is in excess of cell volume and the other 3 granule component. Granules from rats 1 month or less in age tend to be more difficult to isolate with their surrounding membranes intact.
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PMID:Effect of age on mast cell granules. 723 98

The soluble granule chymase, rat mast cell protease-II (RMCP-II), is abundantly expressed in intestinal mucosal mast cells (MMC) but its function is not known. One hypothesis is that RMCP-II degrades the epithelial basement membrane and promotes the loss of enterocytes typically associated with type I hypersensitivity reactions in the rat. To test this hypothesis more directly, ex vivo perfusion of the cranial mesenteric artery and jejunal lumen was used to monitor the anaphylactic release of RMCP-II and its effects on mucosal permeability and epithelial integrity. Within 2 min of intravascular challenge with soluble adult Nippostrongylus brasiliensis worm antigen there was a 1,000-fold (P < 0.02) increase in the concentration of RMCP-II in the vascular perfusate from the jejunum of Nippostrongylus-sensitized rats but not the controls. Similarly, translocation of RMCP-II into the gut lumen increased 10-fold (P < 0.02) after 2 min only in worm antigen-challenged immune rats. Using an identical protocol, but incorporating Evans blue-labeled human serum albumin (EB-HSA) in the vascular perfusate, the timing of the release of RMCP-II into the two compartments was very similar to the first experiment and furthermore the translocation of EB-HSA increased 18-fold (P < 0.05) after 4 min in sensitized rats challenged with worm antigen. To examine the effects of RMCP-II more directly 1 mg of the highly purified chymase was introduced into the cranial mesenteric artery in ex vivo perfused normal rats. A significant (P < 0.05) 70-fold increase in concentration of RMCP-II in jejunal perfusate occurred after 6 min. In a repeat dose-response experiment, infusion of 0.375, 0.75, or 1.5 mg of RMCP-II, together with EB-HSA, established that the cumulative amounts of RMCP-II and EB-HSA translocated from the vasculature to the gut lumen in each perfusion (during the 10-min period of RMCP-II infusion) were significantly correlated. Analysis of intestinal perfusates by SDS-PAGE and by Western blotting using monoclonal anti-RMCP-II antibody confirmed that there was a concomitant translocation of both the protease and EB-HSA into the gut lumen. Histological evaluation of the mucosa failed to reveal any significant morphological change in any of the experiments. The rapid development of macromolecular leak, its association with the translocation of RMCP-II, and the absence of gross epithelial lesions, suggest for the first time that a mast cell granule chymase increases epithelial permeability via a paracellular route and implies that the substrate may be a protein, or proteins, in the epithelial junctional complex.
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PMID:Release of the mucosal mast cell granule chymase, rat mast cell protease-II, during anaphylaxis is associated with the rapid development of paracellular permeability to macromolecules in rat jejunum. 750 33

Rat basophilic leukemia (RBL) cells are considered to be similar to bone-marrow derived mast cells and to mucosal mast cells (MMC), the latter of which may be involved in inflammatory bowel diseases. RBL cells are not able to accumulate histamine and secretory granules under regular growing conditions. Here we show that the flavonoid quercetin, which inhibits mast cell secretion of histamine, also inhibited RBL cell proliferation and constitutive histamine release while it induced synthesis of rat mast cell protease (RMCP) II and triggered processes leading to accumulation of secretory granules. Cell viability was also retained in the presence of quercetin, whereas untreated cells did not survive past 6 days of growth. Quercetin did not affect the expression of mRNA for alpha-subunit of immunoglobulin E (IgE) receptor, but led to increased expression of mRNA for, and synthesis of RMCP II, which is a marker protein for MMC. Many of these granules showed metachromasia with toluidine blue after 3 days of growth, stained red with alcian blue counterstained with safranin after 8 days of growth, and contained electron dense material. Our results suggest that RBL cells have the capacity to progress to a more mature state and may lend themselves to further analysis of a growth regulator(s) with action similar to that of quercetin.
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PMID:Quercetin-induced expression of rat mast cell protease II and accumulation of secretory granules in rat basophilic leukemia cells. 750 28

The mast cell protease inhibitor trypstatin was purified from rat peritoneal mast cells (Kido, H., Yokogoshi, Y., and Katunuma, N. (1988) J. Biol. Chem. 263, 18104-18107). We noticed that trypstatin could possibly be identical with the second half of inter-alpha-trypsin inhibitor light chain (ITI-LC), because only 5 amino acid residues of trypstatin are different from the sequence deduced from the recently reported rat ITI-LC mRNA. Southern blot analysis revealed that a 170-base pair probe corresponding to the second half of rat ITI-LC hybridized to the digested rat genomic DNAs only at single bands even in low stringency conditions. Similarly, a 170-base pair probe corresponding to the human counterpart, which differs by 10 deduced amino acids from the rat probe, also hybridized to the digested rat genomic DNAs only at single bands at the same positions and same conditions. These results suggest that rat trypstatin is genetically identical with rat ITI-LC. ITI-LC/trypstatin mRNA was not detected in rat peritoneal mast cells by RNA blot nor by reverse transcription-polymerase chain reaction analysis. Since trypstatin was purified from rat peritoneal mast cells and the cells were immunohistochemically positive with anti ITI-LC antibody, ITI-LC/trypstatin may be taken up into mast cell granules from the serum but may not be generated by mast cells themselves.
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PMID:Mast cell protease inhibitor, trypstatin, is a fragment of inter-alpha-trypsin inhibitor light chain. 750 21

Although interleukin-4 (IL-4) in mice is known to augment the proliferation of mast cells and to modulate the expression of certain mast cell protease transcripts, its effect on human mast cells is less well understood. The current study examined the effects of recombinant human IL-4 (rhuIL-4) on stem cell factor (SCF)-dependent fetal liver-derived human mast cells in liquid culture. In no case did rhuIL-4 augment proliferation of mast cells. rhuIL-4 selectively inhibited certain aspects of the development of mast cells in cultures of fetal liver cells with rhuSCF. These include lower numbers and percentages of cells expressing tryptase and surface Kit, smaller cells, and lower contents of cells for tryptase, histamine, and Kit. Development of metachromasia was not attenuated. The downregulation of Kit, the surface receptor for SCF, is probably a critical factor, because cells lacking this molecule would not be able to respond to SCF. In contrast to mast cell progenitors, mast cells already developed in vitro from fetal liver cells are relatively resistant to rhuIL-4, but are still dependent for survival on the presence of rhuSCF.
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PMID:Interleukin-4 inhibits the expression of Kit and tryptase during stem cell factor-dependent development of human mast cells from fetal liver cells. 752 Jul 76

Bruton tyrosine kinase (EC 2.7.1.112) [Btk, encoded by Btk in mice and BTK in humans (formerly known as atk, BPK, or emb)], which is variously mutated in chromosome X-linked agammaglobulinemia patients and X-linked immunodeficient (xid) mice, has the pleckstrin homology (PH) domain at its amino terminus. The PH domain of Btk expressed as a bacterial fusion protein directly interacts with protein kinase C in mast cell lysates. Evidence was obtained that Btk is physically associated with protein kinase C in intact murine mast cells as well. Both Ca(2+)-dependent (alpha, beta I, and beta II) and Ca(2+)-independent protein kinase C isoforms (epsilon and zeta) in mast cells interact with the PH domain of Btk in vitro, and protein kinase C beta I is associated with Btk in vivo. Btk served as a substrate of protein kinase C, and its enzymatic activity was down-regulated by protein kinase C-mediated phosphorylation. Furthermore, depletion or inhibition of protein kinase C with pharmacological agents resulted in an enhancement of the tyrosine phosphorylation of Btk induced by mast cell activation.
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PMID:The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C. 752 30

The ability of four drugs with anti-allergic action to modulate the uptake of bystander protein, lactulose/rhamnose permeability ratios and mast cell activation was studied in rats presensitized with egg albumin in alum and challenged intraduodenally with the same antigen. Beclomethasone dipropionate (BDP) and nedocromil both significantly reduced the uptake of the bystander protein, bovine serum albumin (P < 0.002 and P > 0.02 respectively). BDP also significantly reduced sugar permeability (P < 0.01). In animals with elevated lactulose/rhamnose permeability ratios we confirmed our earlier observation of a significant correlation between levels of the specific mucosal mast cell protease Rat Chymase II (RChyII-previously known as RMCPII) and the sugar ratios. None of the drugs had any influence on the levels of mast cell protease II released following challenge and there was no correlation between the histological light microscopic appearance of the mast cells and the experimental treatment administered. Our results suggest that in the gut the pharmacological effect of anti-allergic drugs may be complex. Some, such as nedocromil, appear to act only on the mechanisms underlying increased protein uptake whereas others, such as BDP, appear to abrogate both increased protein uptake and increased sugar permeability.
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PMID:Experimental intestinal hypersensitivity. Effect of four anti-allergic drugs on protein uptake, permeability to sugars and mucosal mast-cell activation. 755 48

In an effort to identify genes that are differentially regulated during mast cell development, subtracted cDNA prepared from wild-type murine P815 mastocytoma cells and a P815 subline that exhibits properties of mast cell differentiation was used to screen mast cell cDNA libraries. Several known mast cell-specific cDNAs were isolated including mast cell carboxypeptidase A (MC-CPA), murine mast cell protease-5 (MMCP-5), and gp49. A novel cDNA, designated Tbc1, was identified that showed differential expression in the two mast cell lines. The amino acid sequence predicted from the cDNA contains a 200 amino acid domain that is homologous to regions in the tre-2 oncogene and the yeast regulators of mitosis, BUB2 and cdc16. The N-terminal region contains a number of cysteine and histidine residues, potentially encoding a zinc finger domain. Tbc1 is a nuclear protein and is expressed in highest levels in hematopoietic cells, testis and kidney. Within these tissues, expression of Tbc1 is cell- and stage-specific. Based on sequence similarity, pattern of expression and subcellular localization, Tbc1 may play a role in the cell cycle and differentiation of various tissues.
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PMID:Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16. 756 74

Rat mast cell protease 1 (RMCP-1) is a chymotrypsin-like serine protease (chymase) that is specifically expressed by connective-tissue-type mast cells. It is stored in the secretory granules of the cells in a complex with heparin proteoglycan, and the chymase/heparin proteoglycan complexes are released following mast cell activation. The present study was undertaken to examine if the association with heparin proteoglycan influenced the regulation of RMCP-1 by various macromolecular protease inhibitors. Endogenous mast cell heparin proteoglycan was shown to significantly block the inhibition of RMCP-1 by the serpins alpha 1-protease inhibitor and alpha 1-antichymotrypsin, as well as the inhibition by alpha 2-macroglobulin, soybean trypsin inhibitor and plasma. The blocking of protease inhibition showed an optimum at a RMCP-1/proteoglycan ratio of 5:1 (by mass), corresponding to approximately 80 RMCP-1 molecules bound/proteoglycan molecule. Chymase activity present on intact peritoneal mast cells, i.e. present in its native complex with heparin proteoglycan, was also shown to be largely resistant to inhibition by alpha 1-antichymotrypsin and alpha 1-protease inhibitor. Heparin 10-saccharides and 20-saccharides were inefficient in preventing the interaction of RMCP-1 with alpha 1-antichymotrypsin, whereas pig mucosal heparin (approximately 50 monosaccharide units) blocked protease inhibition. We have previously shown that heparin potentiates the catalytic activity of RMCP-1 and, in the present study, we show that the mechanism for chymase activation involves a sixfold reduction of the Km,app value of RMCP-1 for the chromogenic substrate S-2586. Thus, the association of mast cell chymase with heparin proteoglycan may serve both to potentiate the catalytic activity of the enzyme and to increase the life-span of the chymases by preventing their inhibition after exocytosis.
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PMID:Regulation of rat mast cell protease 1 activity. Protease inhibition is prevented by heparin proteoglycan. 758 46

By using the combination of reverse-transcription PCR and rapid amplification of cDNA ends methods, a cDNA encoding mast cell tryptase was successfully cloned from the small intestine of Mongolian gerbil, Meriones unguiculatus, infected with Nippostrongylus brasiliensis. The cDNA was 1219 bp long including 810 bp of an open reading frame. Based on the deduced amino acid sequences of known mast cell tryptases of other species, the gerbil mast cell tryptase (gMCT) was highly similar to mouse mast cell protease (mMCP)-7, and seems to be translated as a prepro-enzyme with 25 amino acids of signal and activation peptides and 245 amino acids of mature enzyme. The gMCT mRNA was preferentially transcribed in the intestinal mucosa and to a far lesser extent in the connective tissue such as skin and tongue. Moreover, kinetic study after infection revealed that the amount of gMCT mRNA in the small intestine correlated well with the degree of intestinal mastocytosis. Throughout the course of infection, enzyme-histochemically detectable tryptase activity was limited to mucosal mast cells. Since mucosal mast cells of other rodents, including mice and rats, do not express tryptases, this is the first report of rodent mast cell tryptase expressed in the intestinal mucosa.
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PMID:Cloning of the cDNA encoding mast cell tryptase of Mongolian gerbil, Meriones unguiculatus, and its preferential expression in the intestinal mucosa. 763 11


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