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)

Serine proteases in mast cell granules, such as chymase, atypical chymase, and tryptase, which are major proteins in the granules, may play important roles in the process of immunoglobulin E (IgE)-mediated degranulation and in pathobiological alterations in tissues. Indeed, inhibitors of chymase, substrate analogs, and antichymase F(ab')2, but not inhibitors of tryptase, markedly inhibited histamine release induced by IgE-receptor bridging but not that induced by Ca ionophore. In contrast, inhibitors of metalloprotease inhibited histamine release induced not only by IgE-receptor bridging but also by Ca ionophore. These results suggest that chymase and metalloprotease are involved at different steps in the process of degranulation. The extents of inhibition of histamine release were closely correlated with the amounts of the inhibitors of chymase accumulated in the granules. After degranulation, the released proteases may in part contribute to pathobiological alterations in allergic disorders through generations of C3a anaphylatoxin and thrombin by human and rat tryptase, respectively, and those of angiotensin II and a chemotactic factor of neutrophils by human and rat chymase, respectively. Moreover, chymase and atypical chymase from rat were shown to destroy type IV collagen, and human tryptase was found to hydrolyze various plasma proteins, such as fibrinogen and high-molecular-weight kininogen. The biological activities of tryptase and chymase from rat may be regulated by their dissociation from and association with trypstatin, an endogenous inhibitor of these proteases.
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PMID:Biological functions of serine proteases in mast cells in allergic inflammation. 246 15

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

Complementary DNAs (cDNAs) encoding alpha 1-microglobulin (alpha 1mG)/bikunin, also known as inter-alpha-inhibitor (I alpha I) light chain, were cloned from liver extracts of the Mongolian gerbil, Meriones unguiculatus, and the Syrian golden hamster, Mesocricetus auratus, by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends methods. From the deduced amino-acid sequences of alpha 1mG/bikunin of gerbil and hamster, the basic molecular structure of the proteins seemed to be well-conserved. However, near the proposed sequence of proteinase inhibitory sites of two Kunitz domains in the bikunin part, variable regions composed of three amino acids each were observed between species, including rodents. Since the second half of bikunin is genetically identical with the mast cell proteinase inhibitor, trypstatin, the bikunin of each animal may have distinct inhibitory activity against mast cell proteinases.
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PMID:Sequencing of cDNAs encoding alpha 1-microglobulin/bikunin of Mongolian gerbil and Syrian golden hamster in comparison with man and other species. 752 51

A cDNA encoding alpha 1-microglobulin (alpha 1mG)/inter-alpha-trypsin inhibitor light chain (ITI-LC) was cloned from mouse liver by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. Sequence analysis of the cDNA showed that the basic molecular structure of the proprotein was similar to that in other animals, so that two mature proteins, alpha 1mG and ITI-LC, could be produced from the proprotein translated from the mRNA. Since ITI-LC is known as a positive acute phase reactant and since ITI-LC is genetically identical with mast cell proteinase inhibitor, trypstatin, we examined the mRNA level in the liver of parasite-infected mice showing extensive mastocytosis. The mRNA level was, however, not significantly changed during inflammatory processes, except for a slight increase on day 8 post-infection.
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PMID:cDNA sequencing of mouse alpha 1-microglobulin/inter-alpha-trypsin inhibitor light chain and its expression in acute inflammation. 753 61

We recently reported that the rat mast cell proteinase inhibitor trypstatin is genetically identical with the second half of inter-alpha-trypsin inhibitor light chain (ITI-LC), also known as bikunin or urinary trypsin inhibitor (UTI). In this study, therefore, immunoreactivities of mast cells of various human tissues were examined with three antibodies, anti-human ITI-LC, anti-ITI, which recognizes mainly heavy chains or the sugar moiety of ITI, and anti-alpha 1-microglobulin (alpha1mG). ITI-LC immunoreactivity was strongly found in mast cells in the connective tissues of various organs except for those of the propria mucosae of small intestine. Neither anti-ITI antibody nor anti-alpha1mG antibody reacted with mast cells in various tissues. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, alpha1mG/ITI-LC mRNA was not detected in the skin and tongue, and only weakly in small intestine, although ITI-LC immunoreactivity was strongly detected in these tissues. Furthermore, the mRNA was not expressed in cultured human mast cells. These results suggest that ITI-LC protein is stored in the granules of human connective tissue mast cells, though is not produced by them.
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PMID:Immunohistochemical demonstration of inter-alpha-trypsin inhibitor light chain (bikunin) in human mast cells. 1039 92