[Lung fibroblast growth-stimulating activity of serine protease].
We compared lung fibroblast growth-stimulating activity (FGA) of several serine proteases including thrombin in vitro, and examined the mechanism of FGA. FGA was measured by incorporation of 3H-thymidine into lung fibroblasts (IMR-90). The activities of the enzymes were measured by spectrofluorometric method with synthetic peptides specific for each enzyme, and these enzymes were added to the assay system for FGA at concentrations of 7 x 10(0)-7 x 10(5) unit/ml. Human thrombin, bovine trypsin and bovine alpha-chymotrypsin showed clear FGA, but that of alpha-chymotrypsin was lower than those of thrombin and trypsin. On the other hand, porcine pancreatic elastase and human neutrophil elastase did not show any FGA, and had a cytotoxic effect on fibroblasts. A specific low molecular-weight thrombin inhibitor, argatroban (MW. 562), inhibited not only the enzyme (peptidolytic) activity of thrombin, but also its FGA at the same concentration. These results suggest that serine proteases can be classified into at least two groups, showing FGA and cytotoxic activity, respectively, and that the FGA of the former group is mediated by their catalytic (enzymatic) action.
Ueta
Y
Y
Third Department of Internal Medicine, School of Medicine, University of Tokushima.
Yasuoka
S
S
Ogura
T
T
D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002384:Catalysis; D002417:Cattle; D002478:Cells, Cultured; D010450:Endopeptidases; D005347:Fibroblasts / Q000187:drug effects; D018093:Gelatinases; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000209:etiology; D012697:Serine Endopeptidases / Q000494:pharmacology* / Q000502:physiology; D013552:Swine; D000099167:Fibroblast Activation Protein Alpha
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D006133:Growth Substances; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha