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)

Mouse mast cell protease (MMCP) mRNA expression was examined by in situ hybridization histochemistry. Peritoneal mast cells (PMCs) of WBB6F1-(+/+) mice expressed MMCP-2, MMCP-4, MMCP-5, and MMCP-6 mRNAs, but did not express MMCP-1 mRNA. When proliferation of PMCs was induced by culturing them in methylcellulose with T cell-derived cytokines, cells in mast cell colonies expressed MMCP-1 mRNA. These mast cells were transferred to a suspension culture to induce further proliferation. The phenotype of the resulting PMC-derived cultured mast cells was similar to that of bone marrow-derived cultured mast cells. When 10(5) PMC-derived cultured mast cells or 10(5) bone marrow-derived cultured mast cells were injected into the stomach wall of mast cell-deficient WBB6F1-W/Wv mice, mast cells that appeared in the mucosa and muscularis propria were similar to mast cells in the stomach of intact WBB6F1-(+/+) mice, indicating the injected cells adapted to a new tissue environment. In contrast, when 10(5) PMCs were injected into the stomach wall of WBB6F1-W/Wv mice, the injected PMCs did not adapt to the mucosa. When 20 PMCs were injected, they proliferated and adapted to the mucosal environment. The present results suggest that PMCs adapt to new environments when proliferation occurs before redifferentiation.
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PMID:Alteration of protease expression phenotype of mouse peritoneal mast cells by changing the microenvironment as demonstrated by in situ hybridization histochemistry. 973 41

To study the kinetics and the phenotype of the mast cells (MC) arising during infection with the nematode Nippostrongylus brasiliensis, monospecific cDNA probes for nine different MC proteases were used in a Northern blot analysis of RNA from the small intestine of infected rats. The expression was analyzed at four individual time points during infection, day 0 (before infection), and days 7, 12 and 16 post infection. A dramatic increase in mRNA for rat mast cell protease (RMCP)-2, the major mucosal MC protease in the rat, was observed, beginning around day 7 after infection and peaking around day 12. At day 16 the expression was already beginning to decline. An almost identical pattern of mRNA expression was detected for the RMCP-8 subfamily of rat MC proteases (RMCP-8, -9 and -10) and for two additional rat serine proteases, the chymases RMCP-3 and -4. No simultaneous increase in the proteases known to be expressed preferentially by mature connective tissue MC (RMCP-1, -6 and -7) was observed. This is consistent with our finding that the expansion of MC in the intestines of parasite-infected animals was limited, almost exclusively, to the mucosal MC population. However, a minor increase in RMCP-5 and MC carboxypeptidase A (CPA) mRNA was detected at day 12 after infection, suggesting a derivation of mucosal MC from an expanding RMCP-5- and CPA-positive population of MC precursors.
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PMID:A kinetic analysis of the expression of mast cell protease mRNA in the intestines of Nippostrongylus brasiliensis-infected rats. 984 15

The dynamics of intestinal mucosal mast cells and the major mucosal mast cell protease were followed during the course of laboratory infections of mice with Hymenolepis diminuta and H. microstoma. The effects of the drug cyclosporin A (CsA), which is both immunosuppressive and selectively anthelmintic depending upon dose regime, were determined. In H. diminuta infections worm expulsion occurred around day 9 and coincided with peak mastocytosis and peak mMCP-I concentrations in tissues and serum. Immunosuppressive treatment with CsA prevented worm expulsion, permitting some individuals to reach maturity, and abrogated mast cell proliferation and mMCP-I production and release. By contrast, H. microstoma infections persisted for 64 days in spite of a considerable mastocyosis in both intestine and bile duct tissues accompanied by a high level of mMCP-I in tissues and serum. A subimmunosuppressive regime of CsA had only limited effects on worms and mast cell numbers and activity. Together these data shed light on the variable mast cell response to gastrointestinal infections and on the potential significance of parasite location in evasion of mast cell action. Use of CsA reveals the contributions of both T cell-dependent mechanisms, including mast cell proliferation and activation, and T cell-independent events in regulating intestinal helminth infections.
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PMID:Mucosal mast cell responses and release of mast cell protease-I in infections of mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A. 1020 95

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). Mutant alleles of mi, Mior, and Miwh are deletion or point mutation of the basic domain by which MITF binds DNA. The basic domain also has nuclear localization potential. In the present study, we compared the mast cell abnormalities of Mior/Mior and Miwh/Miwh mice with those of mi/mi mice, of which many have been described by us. The number of mast cells in the skin of Mior/Mior suckling mice was remarkably decreased from that observed in mi/mi suckling mice, but the number was normal in the skin of Miwh/Miwh suckling mice. The decrease in skin mast cells was more severe in the mi/mi embryos than in mi/mi suckling mice, but the magnitude of the decrease was comparable between Mior/Mior embryos and Mior/Mior suckling mice. The poor mRNA expression of granzyme B and tryptophan hydroxylase genes was observed in all cultured mast cells (CMCs) derived from the spleens of Miwh/Miwh, Mior/Mior, and mi/mi mice. However, the poor expression of mouse mast cell protease-4 (MMCP-4), MMCP-5, and MMCP-6 was observed only in Mior/Mior and mi/mi CMCs. MITF encoded by Miwh mutant allele (Miwh-MITF) showed deficient but demonstratable DNA binding, but mi-MITF and Mior-MITF did not show any DNA binding ability. Although Miwh-MITF and Mior-MITF showed normal nuclear localization potential, the potential was significantly impaired in mi-MITF. The rank order of mast cell abnormality (mi/mi > Mior/Mior > Miwh/Miwh) appears to be related to the functional abnormality of MITF encoded by each mutant gene.
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PMID:Different effect of various mutant MITF encoded by mi, Mior, or Miwh allele on phenotype of murine mast cells. 1036 Nov 15

It has been reported that infection with Nippostrongylus brasiliensis induces villus atrophy with various histological alterations. In N. brasiliensis-infected rats, villus length in the jejunum was reduced significantly at day 10 p.i., when serum levels of rat mast cell protease (RMCP) II had increased significantly. To determine whether the villus atrophy is associated with enhancement of apoptosis, apoptotic nuclei were labelled using the nick end-labelling method. Numbers of labelled cells were markedly increased in the villus epithelium at 7-10 days p.i., while the numbers returned to normal 14 days p.i. when worms were rejected from the intestine and villus length became normal. Examination of the expression of the adhesion molecule E-cadherin showed granular immunoreactivity in the cytoplasm of atrophic villus epithelium with loss of normal localization to epithelial cell borders. In mast cell-deficient Ws/Ws rats, villus length was reduced as significantly as in +/+ counterparts at day 10 p.i. with marked increases in the numbers of apoptotic cells. These results suggested that villus atrophy was closely associated with enhanced apoptosis and loss of adhesion in epithelial cells. Mast cell activation appears not to be involved in these alterations.
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PMID:Enhancement of apoptosis with loss of cellular adherence in the villus epithelium of the small intestine after infection with the nematode Nippostrongylus brasiliensis in rats. 1046 28

The mi locus encodes a member of the basic - helix - loop - helix - leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Although the bHLH-Zip family transcription factors generally recognize and bind CANNTG motifs, the expression of mouse mast cell protease 6 (MMCP-6) gene is regulated by MITF through the GACCTG motif in the promoter region. The GACCTG motif was partly overlapped the TGTGGTC sequence, which was bound by polyomavirus enhancer binding protein 2 (PEBP2). In the present study, the effect of PEBP2 on the expression of MMCP-6 gene was examined. PEBP2 that is composed of alpha and beta subunits was expressed by mast cell lines and cultured mast cells derived from spleen. The overexpression of dominant negative PEBP2 cDNA reduced the expression of MMCP-6. Moreover, the simultaneous transfection of the plasmid containing MITF cDNA and the plasmid containing PEBP2 cDNA increased the MMCP-6 promoter activity. For the synergistic action of PEBP2 and MITF, the intact GACCTG and TGTGGTC motifs were prerequisite. The PEBP2alphaB1 mutant which lacked the region downstream from the Runt domain did not bind MITF and lost the synergistic function. These results indicated that PEBP2 and MITF synergistically transactivated the MMCP-6 gene and that the region downstream from the Runt domain of PEBP2alphaB1 was essential for the physical and functional interactions with MITF.
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PMID:Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene. 1046 8

Mouse mast cell protease (mMCP) 6 and mMCP-7 are homologous tryptases stored in granules as macromolecular complexes with heparin and/or chondroitin sulfate E containing serglycin proteoglycans. When pro-mMCP-7 and pseudozymogen forms of this tryptase and mMCP-6 were separately expressed in insect cells, all three recombinant proteins were secreted into the conditioned medium as properly folded, enzymatically inactive 33-kDa monomers. However, when their propeptides were removed, mMCP-6 and mMCP-7 became enzymatically active and spontaneously assumed an approximately 150-kDa tetramer structure. Heparin was not required for this structural change. When incubated at 37 degrees C, recombinant mMCP-7 progressively lost its enzymatic activity in a time-dependent manner. Its N-linked glycans helped regulate the thermal stability of mMCP-7. However, the ability of this tryptase to form the enzymatically active tetramer was more dependent on a highly conserved Trp-rich domain on its surface. Although recombinant mMCP-6 and mMCP-7 preferred to form homotypic tetramers, these tryptases readily formed heterotypic tetramers in vitro. This latter finding indicates that the tetramer structural unit is a novel way the mast cell uses to assemble varied combinations of tryptases.
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PMID:Formation of enzymatically active, homotypic, and heterotypic tetramers of mouse mast cell tryptases. Dependence on a conserved Trp-rich domain on the surface. 1061 25

To examine the possible roles of mast cells in the pathogenesis of subcapsular cell hyperplasia (SCH) in the adrenal glands of mice, we investigated the expression of certain cytokines, including stem cell factor (SCF), tumor necrosis factor-alpha (TNF-alpha), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF), and mast cell-specific proteases, such as mouse mast cell protease (mMCP)-2 and mMCP-7. The mRNAs of c-kit (SCF receptor), bFGF, TNF-alpha, mMCP-2, and mMCP-7 were expressed in both the adrenal glands and the mouse bone marrow-derived mast cells (mBMMCs). Immunoreactivities for cytokines (SCF, NGF, TNF-alpha) and proteases (mMCP-2, mMCP-7) were exclusively located in the mast cells in SCH lesions. The immature mBMMCs did not express the mRNAs of SCF and NGF, whereas the mast cells in the SCH lesions showed the expression of SCF and NGF. These findings suggest that SCH may provide a favorable microenvironment for functional maturation of mast cells to produce SCF and NGF, and the mast cells in SCH lesions synthesize SCF and NGF and may, in part, use them in autocrine fashion for their survival and differentiation. Therefore, mast cells may contribute to SCH pathogenesis by producing a range of multifunctional cytokines and proteases.
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PMID:Expression of cytokines and proteases in mast cells in the lesion of subcapsular cell hyperplasia in mouse adrenal glands. 1080 47

Previously, this laboratory identified clusters of alpha-, beta-, and mast cell protease-7-like tryptase genes on human chromosome 16p13.3. The present work characterizes adjacent genes encoding novel serine proteases, termed gamma-tryptases, and generates a refined map of the multitryptase locus. Each gamma gene lies between an alpha1H Ca2+ channel gene (CACNA1H) and a betaII- or betaIII-tryptase gene and is approximately 30 kb from polymorphic minisatellite MS205. The tryptase locus also contains at least four tryptase-like pseudogenes, including mastin, a gene expressed in dogs but not in humans. Genomic DNA blotting results suggest that gammaI- and gammaII-tryptases are alleles at the same site. betaII- and betaIII-tryptases appear to be alleles at a neighboring site, and alphaII- and betaI-tryptases appear to be alleles at a third site. gamma-Tryptases are transcribed in lung, intestine, and in several other tissues and in a mast cell line (HMC-1) that also expresses gamma-tryptase protein. Immunohistochemical analysis suggests that gamma-tryptase is expressed by airway mast cells. gamma-Tryptase catalytic domains are approximately 48% identical with those of known mast cell tryptases and possess mouse homologues. We predict that gamma-tryptases are glycosylated oligomers with tryptic substrate specificity and a distinct mode of activation. A feature not found in described tryptases is a C-terminal hydrophobic domain, which may be a membrane anchor. Although the catalytic domains contain tryptase-like features, the hydrophobic segment and intron-exon organization are more closely related to another recently described protease, prostasin. In summary, this work describes gamma-tryptases, which are novel members of chromosome 16p tryptase/prostasin gene families. Their unique features suggest possibly novel functions.
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PMID:Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families. 1084 16

A serine protease inhibitor, termed TsCEI, was purified from adult-stage Trichuris suis by acid precipitation, affinity chromatography (elastase-agarose), and reverse-phase HPLC. The molecular weight of TsCEI was estimated at 6.437 kDa by laser desorption mass spectrometry. TsCEI potently inhibited both chymotrypsin (K(i) = 33.4 pM) and pancreatic elastase (K(i) = 8.32 nM). Neutrophil elastase, chymase (mouse mast cell protease-1, mMCP-1), and cathepsin G were also inhibited by TsCEI, whereas trypsin, thrombin, and factor Xa were not. The cDNA-derived amino acid sequence of the mature TsCEI consisted of 58 residues including 9 cysteine residues with a molecular mass of 6.196 kDa. TsCEI displayed 48% sequence identity to a previously characterized trypsin/chymotrypsin inhibitor of T. suis, TsTCI. TsCEI showed 36% sequence identity to a protease inhibitor from the hemolymph of the honeybee Apis mellifera. Sequence similarity was also detected with the trypsin/thrombin inhibitor of the European frog Bombina bombina, the elastase isoinhibitors of the nematode Anisakis simplex, and the chymotrypsin/elastase and trypsin inhibitors of the nematode Ascaris suum. The inhibitors of T. suis, an intestinal parasite of swine, may function as components of a parasite defense mechanism by modulating intestinal mucosal mast cell-associated, protease-mediated, host immune responses.
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PMID:Trichuris suis: a secretory chymotrypsin/elastase inhibitor with potential as an immunomodulator. 1086 16


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