Acetyl-LDL stimulates macrophage-dependent plasminogen activation and degradation of extracellular matrix.
The ability of acetyl-LDL to stimulate macrophage-dependent plasminogen activation and degradation of extracellular matrix was examined. We have found that expression of plasminogen activator activity in response to the scavenger receptor ligand varied among cell populations. Exposure to acetyl-LDL stimulated plasminogen activator expression by cells which constitutively released low levels of activator. These include a virally transformed macrophage-like cell line (RAW246.7), concanavalin A and C. parvum-activated macrophages. The stimulation of plasminogen activator activity was independent of cellular lipid accumulation since nonlipoprotein inhibitors of acetyl-LDL binding to the scavenger receptor stimulated activator expression in great excess to that observed with acetyl-LDL. In contrast, acetyl-LDL was unable to induce soluble plasminogen activator activity in cells which normally do not express it. These include a macrophage-like cell line (J774A.1) and resident peritoneal macrophages. Furthermore, acetyl-LDL was unable to modulate the copious secretion of activator by inflammatory macrophages elicited with thioglycolate. When macrophages were tested for their ability to degrade smooth muscle cell derived matrix, solubilization by resident, elicited, and activated cells was variously increased in the presence of plasminogen. Furthermore, exposure to acetyl-LDL enhanced plasmin-dependent degradation by resident cells and activated cells, whereas matrix degradation by elicited cells was unaffected.
Falcone
D J
DJ
Department of Pathology, Cornell University Medical College, New York, New York 10021.
Ferenc
M J
MJ
D000818:Animals; D002417:Cattle; D002460:Cell Line; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism; D006801:Humans; D007106:Immune Sera; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects*; D010958:Plasminogen / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D007106:Immune Sera; D008077:Lipoproteins, LDL; D011134:Polysaccharides; C032629:acetyl-LDL; D010958:Plasminogen; C007789:fucoidan; D014568:Urokinase-Type Plasminogen Activator; D005944:Glucosamine