Co-operation between plasmin and elastase in elastin degradation by intact murine macrophages.
Intact, thioglycollate-stimulated murine macrophages cultured on an insoluble [3H]-elastin substratum progressively hydrolysed the elastin. Cell lysates had little activity. We compared the effect of various proteinase inhibitors on elastinolysis by either live cells or cell-free, elastase-rich conditioned medium. Only known inhibitors of macrophage elastase blocked the activity of elastase-rich cell-conditioned medium whereas inhibitors of cathepsin B also suppressed intact cell activity. Serum proteinase inhibitors blocked cell-derived soluble elastase activity but not intact cell elastolytic activity. We also observed that plasminogen added to the cell cultures markedly increased elastinolysis by live macrophages or cell-free elastase-rich medium. Purified plasmin alone had no measurable effect on native elastin. Additional experiments indicated that the plasmin enhancement was due to elastin-dependent activation of latent macrophage elastase. These results indicate that live macrophage elastinolysis is a co-operative process involving multiple proteinases, especially a cysteine proteinase(s) and elastase. Plasmin may be a physiological activator of latent macrophage elastase.
D000818:Animals; D002478:Cells, Cultured; D004549:Elastin / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D010196:Pancreatic Elastase / Q000378:metabolism*; D010958:Plasminogen / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013864:Thioglycolates / Q000494:pharmacology
D011480:Protease Inhibitors; D013864:Thioglycolates; C017487:2-mercaptoacetate; D010958:Plasminogen; D004549:Elastin; D010196:Pancreatic Elastase; D005341:Fibrinolysin