Co-operation between plasmin and elastase in elastin degradation by intact murine macrophages

• Published in: Biochemical journal 1984-09, Vol.222 (3), p.721-728
• Main Authors: Chapman, Jr, H A, Stone, O L
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Elastin - metabolism; Enzyme Activation - drug effects; Female; Fibrinolysin - metabolism; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred C3H; Pancreatic Elastase - metabolism; Plasminogen - pharmacology; Protease Inhibitors - pharmacology; Thioglycolates - pharmacology
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2220721

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.