Disease relevance of Mcpt1

• Mast cell protease 5 mediates ischemia-reperfusion injury of mouse skeletal muscle [1].
• The soluble beta-chymases mouse mast cell protease-1 (mMCP-1) and rat mast cell protease-II are predominantly expressed by intestinal mucosal mast cells (IMMCs) and may promote mucosal epithelial permeability when released during intestinal allergic hypersensitivity responses [2].
• The attenuated expulsion of the parasite by IL-9 neutralization was not accompanied by changes in goblet cell hyperplasia or the MMCP-1 level [3].
• FcRgamma(-/-) mice had significantly higher egg counts (P<0.01) and numbers of adult worms (P<0.05) than FcRgamma(+/+) mice, but mastocytosis and serum MMCP-1 release were comparable [4].
• In conclusion, mMCP-1 transcription, storage and secretion occur constitutively in normal BALB/c jejunum but this basal secretion is up-regulated during nematode infection, suggesting both a physiological and pathological function for this protease [5].

High impact information on Mcpt1

• Neither worm fecundity nor worm burdens were altered in Nippostrongylus-infected mMCP-1(-/)- BALB/c mice [6].
• CONCLUSIONS: These results imply that mast cells may contribute to the induction of protective Th2 responses and, importantly, that the intestinal inflammation associated with gastrointestinal helminths is partly mediated by mMCP-1 [7].
• Additionally, levels of TNF-alpha and nitric oxide were significantly reduced in both W/Wv and mMCP-1 deficient mice [7].
• In vivo, this immunization completely abrogated the increase in mast-cell protease-1 levels as well as the eosinophilia observed in mice after implantation of an IL-9-secreting tumor [8].
• Supplementation of the same three cytokines with transforming growth factor-beta1 (TGF-beta1; 1 ng/mL) resulted in substantially enhanced expression (6 micrograms/10(6) mBMMC) and extracellular release (2 micrograms/mL of culture supernatant) of mMCP-1 [9].

Chemical compound and disease context of Mcpt1

• We examined the temporal distribution and phenotype of mast cells during intestinal schistosomiasis in mice, using antibodies directed against histamine, a general mast cell marker, against mouse mast cell protease-1 (MMCP-1), a mucosal mast cell (MMC) marker, and against tryptase, a predominantly connective tissue mast cell (CTMC) marker [10].
• Enteric expression of the integrin alpha(v)beta(6) is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1 [11].

Biological context of Mcpt1

• 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 [12].
• The 5' regulatory regions of MMCP-1 and MMCP-L share a remarkably high degree of sequence identity (98%), starting 10 base pairs downstream of exon 1 and extending to the end of the presently sequenced region at position -1347 of the MMCP-1 gene [13].
• KITG559 and KITV814 also influenced the transcriptional phenotype of mouse mast cell proteases (MMCP) in IC-2 cells [14].
• A region of approximately 4 kb covering the five exons and 930 bp 5' and 280 bp 3' flanking sequences of the gene for MMCP-1 was characterized by nucleotide sequence analysis [15].
• The purpose of this study was to determine the kinetics of mMCP-1 transcription and expression in vivo during nematode-induced IMMC hyperplasia [5].

Anatomical context of Mcpt1

• 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 [16].
• The MMCP-1 is expressed only at the mucosal mast cell stage and 5 only in mast cells of the connective tissue mast cell stage [15].
• Whereas mMCP-2, -4, and -5 were transcribed normally, there was no transcription of the mMCP-1 gene in null (-/-) mice, nor was mature mMCP-1 protein detected in (-/-) jejunal mucosa [2].
• Mucosal mast cell (MMC) responses were assayed by in situ intestinal mast cell counts in stained histological sections of the jejunum and by measuring mouse mast cell protease 1 (MMCP-1) release in serum using sandwich enzyme-linked immunosorbent assay [4].
• Mastocytosis, MMCP-1, and the secretion of cytokines by mesenteric lymph node cells, following stimulation in vitro by Con A, were also more intense initially in SWR mice [17].

Associations of Mcpt1 with chemical compounds

• IL-10 induces transcription of the gene for mouse mast cell protease-1, a serine protease preferentially expressed in mucosal mast cells of Trichinella spiralis-infected mice [18].
• IL-6-deficient mice had significant serum levels of mast cell mediators, histamine and mast cell protease 1, following infection [19].
• MMCP-1 expressing MMCs were predominantly present in the mucosa during the acute phase [8 weeks postinfection (p.i.)], while tryptase and histamine immunoreactivity demonstrated that two subsets of CTMCs were predominantly present in the outer muscle layer at 15 weeks p.i. (chronic phase) [10].
• Mouse mast cell protease-1 cleaves angiotensin I to form angiotensin II [20].
• Effective production of MMCP-1 together with specific IgE and IgG1 suggests a breakdown in oral tolerance to the allergen [21].

Regulatory relationships of Mcpt1

• CONCLUSION: The culture conditions that promote mMCP-1 expression and release by MMC homologues also promote the expression and release of CCL2 [22].
• The normally down-regulatory functions of TGF-beta1 in haematopoiesis are superseded in this culture system by its ability to promote the early expression of alphaE and mMCP-1 [23].

Other interactions of Mcpt1

• Biochemical and immunological characterization of multiple glycoforms of mouse mast cell protease 1: comparison with an isolated murine serosal mast cell protease (MMCP-4) [12].
• The amino acid identity was of 74% with RMCP2, and of 76%, 65% and 90% with the mouse proteases MMCP1, MMCP2 and MMCP4, respectively [24].
• As the key cytokine mediating differentiation of mouse mast cell protease-1-expressing MMC homologues in vitro, TGF-beta1 was considered a likely candidate for regulation of the integrins that facilitate intraepithelial migration of MMC [25].
• Time course analyses revealed early (within 48 h of infection) induction of Siat4c, Sprr2A, and Relmbeta and later (within 120 h) induction of Mcpt-1 and -2 [26].
• RESULTS: mMCP-1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex [22].

Analytical, diagnostic and therapeutic context of Mcpt1

• Mouse mast cell protease (MMCP) mRNA expression was examined by in situ hybridization histochemistry [16].
• 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 [12].
• Molecular cloning of rat mast cell protease 1 and development of specific probes for its gene transcript [24].
• The intracellular distribution of mMCP-1 and CCL2 was examined by confocal microscopy [22].

References