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The spent medium of stimulated peritoneal macrophages coqtains a factor or factors that induce the de novo synthesis of collagenase and neutral protease(s) in primary cultures of articular chondrocytes. The synthesis of this inducing factor by stimulated macrophages is inhibited by cycloheximide, indicating that the factor is a protein. The inducing factor is heat stable and stable to tryspin treatment, but it is partially inactivated on treatment to pH 2.0. The inducing factor is not retained 04 concanavalin Sepharose, is staple to reductive alkylation, and has an apparent molecular weight of a p proximately 30,OOO. Addition of the inducing factor to cartilage slices also results in the synthesis of both collagenase and neutral protease by the slices. Both of these enzymes synthesized by chondrocytes are in the latent form and are activated by either trypsin or plasmin. The neutral protease (MW 22,000) is a metalloprotease and is inhibited by o-phenanthroline and by D-penicillamine but not by phenylmethane sulfonylfluoride or iodoacetic acid. Induction of these latent en- Submitted for publication August 6, 1979; accepted in revised form December 26, 1979. zymes in chondrocytes occurs between 8 and 16 hours after exposure to the inducing factor and is completely blocked by cycloheximide. The spent medium of stimulated lymphocytes (concanavalin A) does not induce the synthesis of these enzymes in chondrocytes, suggesting that the synthesis of the inducing factor may be a prop erty specific to stimulated macrophages.Immunologic disturbances leading to the infiltration of mononuclear and polymorphonuclear cells into the synovium are a characteristic feature of inflammatory joint disease (1). It has been postulated that these cells contribute to the breakdown of articular collagen and proteoglycans that is observed in the disease. This destruction of the matrix can occur by at least two mechanisms. In one mechanism, intracellular neutral proteases and collagenase of the polymorphonuclear cells are released in the synovium and lead to the enzymatic degradation of the cartilage matrix ( 2 4 ) . A second mechanism involves the interaction between the various cell types in the synovium leading to the synthesis of collagenase. Dayer et a1 (5,6) have shown that products synthesized by stimulated lymphocytes can activate synovial cells to synthesize abnormal levels of collagenase. Products of stimulated lymphocytes can also interact with macrophages and result in the synthesis of collagenase by the latter cells (7).Cell-cell interactions between mononuclear cells and chondrocytes have not been investigated in detail. In a recent preliminary communication by Phadke et a1

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