Biological functions of serine proteases in the granules of rat mast cells.
The effects of specific low- and high-molecular weight inhibitors of chymase and tryptase and F(ab')2 of antichymase on histamine release from activated mast cells were examined. The release of histamine induced by anti-rat immunoglobulin E was markedly inhibited by F(ab')2 fragments of antichymase and the low-molecular weight inhibitor of chymase chymostatin, whereas release of histamine induced by calcium ionophore A23187 was inhibited only by chymostatin. Neither the inhibitor nor the antibody affected histamine release induced by compound 48/80. These results suggest that two main chymotrypsin-type proteases are involved in process of degranulation: one is chymase, which acts at a step before calcium entry, and the other is an unidentified protease, which acts at a step after calcium entry. These results are summarized in Figure 8. After degranulation, released chymase remains associated with the cell surface while released tryptase was found in the extracellular milieu. Tryptase converted bovine prothrombin to thrombin, as shown by increase in thrombin activity with a synthetic substrate, t-butyloxy-carbonyl-Val-Pro-Arg-4-methyl-coumaryl-7-amide. The apparent Km value toward prothrombin was relatively low (2.3 microM), suggesting that tryptase contributes to blood coagulation or the process of fibrosis in tissues. The proteolytic products of IgG1 produced by chymase had chemotactic activity for neutrophil leukocytes in vitro and in vivo. These findings indicate the possible functions of these proteases after degranulation.
D000818:Animals; D053818:Chymases; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D012697:Serine Endopeptidases
D011480:Protease Inhibitors; D007073:Immunoglobulin E; D011516:Prothrombin; D010450:Endopeptidases; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D012697:Serine Endopeptidases; D053818:Chymases