The role of plasminogen in interleukin-1 mediated cartilage degradation

Abstract

Explants of 35SO4 labelled rabbit articular cartilage, cultured for 3 days with either 5 X 10(4) rabbit peritoneal cells (PEC) or 1:10 macrophage conditioned medium (MCM), released 30-40% of labelled proteoglycans into the medium while controls released 8-12%. The addition of 1 mM 4 aminophenylmercuric acetate (APMA) or 0.2 U/ml plasminogen increased proteoglycan release to 85%. Similar results were obtained when recombinant human interleukin-1 (IL-1) was used instead of MCM. Further, supernatant from MCM stimulated chondrocytes, incubated with dead cartilage explants for 3 days, did not significantly increase proteoglycan release above the background level of cartilage alone (7-10%), nor did the addition of 5 X 10(4) PEC to cultures of dead cartilage explants plus supernatant from MCM stimulated chondrocytes make any significant difference, indicating that supernatant from MCM stimulated chondrocytes and PEC alone had negligible cartilage proteoglycan degrading activity in these experiments. The inclusion of 0.1 mM APMA or 0.2 U/ml plasminogen in cultures of dead cartilage explants plus supernatant from MCM stimulated chondrocytes, however, increased proteoglycan release to 80-93%, with or without PEC. Our results suggest that plasminogen, activated by a product from IL-1 stimulated chondrocytes, greatly enhanced IL-1 mediated cartilage degradation by activating latent metalloproteinases.