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

In previous work the primary structure of a previously unknown protease was deduced from the sequence of a dog mastocytoma cDNA. The predicted preproprotein shares some features with mast cell tryptases but is no more than 49% identical in sequence to known trypsin-like enzymes, including dog tryptase. This study explores the expression of this protein, termed dog mast cell protease-3 (dMCP-3). A polyclonal Ab was raised to a peptide corresponding to residues 166-181 of the deduced sequence. Anti-dMCP-3(166-181) Ig recognizes dMCP-3 expressed as a CheY fusion protein in Escherichia coli and binds to a approximately 36-kDa protein in extracts of dog mastocytomas. The Ab does not recognize dog tryptase, dMCP-3s closest known relative in mastocytoma cells. When used with fluorescein-conjugated and alkaline phosphatase-conjugated secondary Abs, anti-dMCP-3(166-181) Ig yields punctate cytoplasmic staining in mastocytoma cells, suggesting localization to intracellular granules. Staining is greatly reduced by preincubation with synthetic dMCP-3 peptide, supporting the specificity of the Ab. Immunohistochemical staining of normal dog tissues reveals scattered dMCP-3 reactive cells in skin, intestine, trachea, and lung parenchyma. Double staining with Ab and methylene blue shows that anti-dMCP-3(166-188) Ig recognizes extravascular mononuclear tissue cells with metachromatic granules. In addition, cytoplasmic staining is seen in polymorphonuclear leukocytes within vessels in tissue sections and in leukocytes harvested from blood. Hybridization of dMCP-3 cDNA to dog skin RNA provides further evidence of dMCP-3 gene transcription in normal tissue. Thus, this study provides immunochemical evidence of dMCP-3 expression in dog mast cell tumors, normal tissue mast cells, and neutrophils.
 ...
PMID:Mast cell and neutrophil expression of dog mast cell protease-3. A novel tryptase-related serine protease. 814 4

Eosinophil numbers in peripheral blood and eosinophil potentiating activity (EPA) and sheep mast cell protease (SMCP) in efferent gastric lymph were monitored in lambs during infections with Ostertagia circumcincta. Worm burdens, eosinophil numbers in bone marrow, abomasal mucosa and gastric lymph node, as well as mast cell numbers and SMCP concentrations in mucosa and mucus, were determined in post mortem samples. In naive lambs, high and relatively uniform worm burdens were present 10 days after primary infection and these were associated with only mild blood and tissue eosinophilia. By day 21 worm burdens were markedly lower and more variable. There was more evidence of eosinophil and mast cell accumulation in mucosa, and numbers in bone marrow were also higher than on day 10. However, neither EPA nor SMCP were detectable in lymph. By contrast, EPA and SMCP were present in substantial amounts in draining lymph within 48 h of challenge (secondary) infection of previously exposed lambs. EPA was inversely related to worm burdens recovered on day 10, as were abomasal mucosal and mucus SMCP concentrations. Elevated eosinophil numbers were also consistently detected in blood, bone marrow, mucosa and gastric lymph node. The results suggest that host immune defence against secondary, but not primary, exposure to O. circumcincta involves a rapidly mobilised local inflammatory component.
 ...
PMID:Local eosinophil- and mast cell-related responses in abomasal nematode infections of lambs. 817 55

Heparin is a sulfated glycosaminoglycan, synthesized by connective tissue-type mast cells. Rat mast cell protease 1 (RMCP-1), a chymotrypsin-like serine protease expressed specifically by connective tissue-type mast cells, is recovered in a macromolecular complex with heparin proteoglycan. The heparin.RMCP-1 complexes are stored in the secretory granules of the cells and are released following mast cell activation. We showed previously that dissociation of RMCP-1 from heparin resulted in loss of protease activity, as measured by its ability to inactivate thrombin. In the present report the binding of heparin to RMCP-1 was characterized. Affinity chromatography on heparin-Sepharose showed that RMCP-1 displayed high affinity for heparin, with approximately 1.2 M NaCl being required for elution of RMCP-1 from the affinity matrix. The structural requirements for the binding of heparin to RMCP-1 were investigated. Heparan sulfate, chondroitin sulfate, and dermatan sulfate, three glycosaminoglycans structurally related to heparin, were > or = 80-fold less effective in binding to RMCP-1 than heparin. The 2-O-sulfate, 6-O-sulfate, and N-sulfate groups in heparin were all shown to contribute in the binding. The minimal heparin sequence required for binding to RMCP-1 was found in a 14-saccharide fraction. 14-Saccharide species, obtained after separation by anion exchange chromatography, showed continuously increased binding with increasing anionic charge densities. The 16-18-saccharides were the smallest heparin oligosaccharides capable of accelerating the inactivation of thrombin by RMCP-1.
 ...
PMID:Interaction of heparin with rat mast cell protease 1. 818 50

The pathogenesis of infection with Schistosoma mansoni in rats is distinct from that in mice. Rats are non-permissive hosts and infection is terminated in the liver before egg laying commences whereas the parasites completes its life cycle in mice. Comparison of the mast cell responses in the two species reveals that a pronounced hepatic mastocytosis occurs in the rat and this is concomitant with the demise of the parasite. The majority of recruited hepatic mast cells contain the highly soluble granule chymase, rat mast cell protease-II, which is released systemically into blood during the period of parasite elimination. In contrast, very few mast cells are found in livers of parasitized mice and none contain the soluble granule chymase mouse mast cell protease-1. However, during egg deposition in the gut, an intraepithelial mastocytosis occurs in parasitized mice. These intraepithelial cells are typical mucosal mast cells as determined by their content of mouse mast cell protease-1. Recruitment of mucosal mast cells occurs in the intestinal lamina propria of infected rats soon after the parasites migrate to the liver. These findings suggest that mast cells of the mucosal phenotype are involved in the pathogenesis of the hepatic response to infection in the rat but that, in the mouse, mucosal mastocytosis is associated with intestinal sensitization by egg antigens.
 ...
PMID:Hepatic recruitment of mast cells occurs in rats but not mice infected with Schistosoma mansoni. 820 87

The staining property of skin mast cells changed from Alcian blue+/berberine sulfate- to Alcian blue+/berberine sulfate+ in the skin of normal (+/+) and Wv/Wv mice. In contrast, this change did not occur in the skin of mi/mi mice. Heparin content and histamine content per a mi/mi skin mast cell were estimated to be 34% and 18% those of a +/+ skin mast cell, respectively. The low heparin content of mi/mi skin mast cells seemed to be consistent with the Alcian blue+/berberine sulfate- staining property. Expression of genes encoding mast cell-specific proteolytic enzymes was examined by Northern blotting and in situ hybridization. Messenger RNA of mast cell carboxypeptidase A was expressed most of all by +/+, Wv/Wv, and mi/mi skin mast cells, but mRNA of mouse mast cell protease (MMCP)-6 was expressed by approximately a half of +/+ and Wv/Wv skin mast cells and by only 3% of mi/mi skin mast cells. A significant amount of MMCP-2 mRNA was not expressed in the skin of all +/+, Wv/Wv and mi/mi mice. This shows the presence of at least three phenotypes in skin mast cells of mice: berberine sulfate+/MMCP-6+, berberine sulfate+/MMCP-6-, and berberine sulfate-/MMCP-6-. The in situ hybridization of mRNA of mast cell-specific proteolytic enzymes seemed to be useful to describe abnormalities of mast cell differentiation in the skin of mi/mi mice.
 ...
PMID:Deficient differentiation of mast cells in the skin of mi/mi mice. Usefulness of in situ hybridization for evaluation of mast cell phenotype. 823 51

As assessed by RNA blot analyses with gene-specific probes, we report that the perivascular connective tissue mast cells (CTMCs) in the ear and skin of BALB/cJ mice contain abundant levels of the mouse mast cell protease (mMCP) 7 transcript, in addition to those protease transcripts present in their serosal mast cells (SMCs). High levels of the mMCP-7 transcript also were detected in the ears of WBB6F1/J(-)+/+, WCB6F1/J(-)+/+, WB/ReJ(-)+/+, and WC/ReJ(-)+/+ mice. However, the ears of these four strains and the SMCs from the WCB6F1/J(-)+/+ strain but not the BALB/cJ strain also contained high steady-state levels of the mMCP-2 transcript. The mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMCP-7 transcripts were not detected in the ears of mast-cell-deficient WBB6F1/J-W/Wv and WCB6F1/J-Sl/Sld mice, indicating that mast cells were the source of these protease transcripts in the +/+ animals. When immunohistochemical analyses of serial sections of ear and skin from WBB6F1/J(-)+/+ mice were performed with anti-mMCP-2 IgG and anti-mMCP-5 IgG, the perivascular CTMCs in these tissues were found to express both mMCP-2 and mMCP-5 in their granules. The prominent expression of mMCP-7 in constitutive perivascular CTMCs indicates that this mast cell has an extended protease phenotype relative to the SMCs of the same strains. Further, the perivascular CTMCs and SMCs of the +/+ strains differ from those in BALB/cJ mice in their prominent expression of mMCP-2.
 ...
PMID:Strain-specific and tissue-specific expression of mouse mast cell secretory granule proteases. 827 52

Five highly soluble, chymotrypsin-like, neutral serine proteases, with molecular masses in the range 30-33 kDa, were isolated from Trichinella spiralis-infected mouse small intestine. These enzymes were closely related antigenically on Western blotting and by Ouchterlony double diffusion using a polyclonal, cross-absorbed, sheep antibody raised against mouse mast cell protease-1 (MMCP-1) and on the basis of N-terminal amino acid sequence analysis, were identified as variant forms of MMCP-1. Substrate and inhibitor analysis confirmed that the five variants (MMCP-1 A-E) had similar characteristics, although highly significant (P = 0.025 to P < 0.0001) variations in Km and kcat, were detected. Against human alpha 1-proteinase inhibitor the Ki for MMCP-1C (45 pM) was significantly (P < 0.0001) greater than those for the other proteases (0.76-2.2 pM). The differences in electrophoretic mobility are probably a result of variable glycosylation, since removal of N-linked carbohydrate produced a polypeptide of approx. 28 kDa in each case which was, like the native enzyme, immunoreactive on Western blotting. A much less soluble 28 kDa enzyme was isolated from serosal mast cells and identified as MMCP-4 by N-terminal amino acid sequencing. Like MMCP-1 it has chymotrypsin-like substrate specificities with activity at neutral pH. However, it was antigenically distinct from MMCP-1 and, using sheep anti-MMCP-1, was not detected on Western blotting or by Ouchterlony double diffusion, e.l.i.s.a. or immunohistochemistry. This last technique established that the MMCP-1 variants were uniquely present in enteric mast cells, thereby providing a highly selective means of distinguishing the mucosal and connective tissue mast cell subsets in the mouse.
 ...
PMID:Biochemical and immunological characterization of multiple glycoforms of mouse mast cell protease 1: comparison with an isolated murine serosal mast cell protease (MMCP-4). 836 63

A role for mast cell proteases (RMCP I and II) in the cyclical remodelling of ovarian and uterine tissues of rats was investigated in the oestrous and pregnancy cycles using immunocytochemistry and enzyme-linked immunosorbent assays. The concentrations of RMCP I exceeded that of RMCP II by 100-fold in both tissues, but were always much higher in uteri than ovaries. Most of the protease activity in the uterus was located in the myometrium, whereas it was more focally distributed in the hilus and medulla of the ovary. Protease activity was confined to mast cells identified by metachromatic staining and no single cell contained both proteases. The concentrations of RMCP I and II in the two organs did not fluctuate throughout the 4-day oestrous cycle. Neither were RMCP I concentrations in the uterus altered by administration of diethylstilboestrol to ovariectomized animals, although total amounts per uterus were substantially greater than in the controls. Concentrations of RMCP I were substantially reduced in the uterus after day 6 of pregnancy and rose during the puerperium. The reduction was greater in pregnant than in pseudopregnant horns and tended to be lower in the vicinity of conceptuses than between them. The physiological significance of the lower mast cell protease concentrations is unclear, although their absence may contribute to the decreased protein catabolism during pregnancy.
 ...
PMID:Quantitative and cytochemical studies of mast cell proteases in rat ovaries and uteri in various reproductive states. 841 Aug 27

Tryptase is the major secretory protease of human mast cells and is proposed to be involved in neuropeptide processing and tissue inflammation. Exploration of the biology of tryptase has been hindered by the lack of potent, selective inhibitors. The current study explores the properties of aromatic diamidines as inhibitors of dog and human tryptase. The strongest inhibitors of tryptase in this series are bis(5-amidino-2-benzimidazolyl)methane (BABIM) and (5-amidino-2-benzimidazolyl)-(5-(N,N'-dimethylamidino)-2- benzimidazolyl)methane, which exhibit K(i) values of 1.8 and 1.4 nM, respectively, in blocking the hydrolysis of tosyl-L-Gly-Pro-Lys-4-nitroanilide by human tryptase. These compounds are approximately 10,000-fold more potent than benzamidine, and are the strongest reversible inhibitors of tryptase described to date. Other aromatic mono- and diamidines, including amiloride and pentamidine, are less potent. Nonetheless, they abolish tryptase activity at high inhibitor concentrations. The rank order of tryptase inhibitor potency parallels that of inhibitors tested against trypsin. BABIM, the only highly active member of this series whose potency against other targets has been examined previously, is a far stronger inhibitor of tryptase than of other trypsin-like serine proteases, including those involved with hemostasis, fibrinolysis and the complement system. Therefore, BABIM appears to have selective affinity for tryptase. In addition to inhibiting tryptase-induced hydrolysis of peptide-based chromogenic substrates, BABIM blocks completely the reversal of vasoactive intestinal peptide-induced relaxation of isolated trachea by dog tryptase. Thus, BABIM and related amidines are potent inhibitors of mast cell tryptases that may be useful in exploring mast cell protease biology.
 ...
PMID:Bis(5-amidino-2-benzimidazolyl)methane and related amidines are potent, reversible inhibitors of mast cell tryptases. 843 15

A cDNA encoding rat mast cell tryptase (rMCT) was successfully cloned, and sequenced, from peritoneal cells of Lewis rats infected with Nippostrongylus brasiliensis by the reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends methods. The cDNA was 1,097 base-pairs long, and included 822 base-pairs of an open reading frame. As judged from the deduced amino acid sequence, rMCT is highly homologous to mouse mast cell protease-6, and is considered to be translated as a prepro-enzyme with a 19-amino acid signal peptide, a 10-amino acid activation peptide, and a 245-amino acid mature enzyme. The rMCT mRNA was not detected in peritoneal cells of mast cell-deficient Ws/Ws rats, though it was strongly detected in ones of littermate +/+ and Lewis rats. In addition to in peritoneal mast cells, the rMCT mRNA was detected in the tongue. However, mRNA signals were not detected in the small intestine regardless of N. brasiliensis infection. Nor were mRNA signals detected in RBL2H3 rat basophilic leukemia cells. In the lung, the rMCT mRNA was strongly detected after infection with N. brasiliensis, though it was only faintly detected before infection. These results suggest that the rMCT is basically specific for connective tissue mast cells, but not for mucosal mast cells and that it is up-regulated in the lung during the inflammatory process of a parasitic infection.
 ...
PMID:cDNA sequencing and expression of rat mast cell tryptase. 853 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>