Macrophage Factor that Induces Neutral Protease Secretion by Normal Rabbit Chondrocytes

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Abstract
Normal rabbit-articular chondrocytes secrete very small amounts of degradative enzymes in culture. Rabbit peritoneal macrophages, when activated with lipopolysaccharides, release a factor in the medium which stimulates the chondrocytes to produce significantly high levels of collagenase and other neutral protease for 2-3 days. The soluble mediator from macrophages appears to be a polypeptide with a MW of 13,000-15,000 and can be inactivated by short-term treatment with trypsin or pronase. The enzyme synthesis by chondrocytes can be stimulated to the same extent by repeated addition of the macrophage-medium. The metabolism of chondrocytes is altered due to the presence of this mediator. The cellular proliferation is diminished, while the rates of degradation and biosynthesis of the matrix are increased. In conditions such as osteoarthritis, where the synovial cells may not play an active role in cartilage degradation, the proteases may be produced by the cartilage cells themselves after stimulation by macrophage-derived mediators. These intrinsic enzymes may be responsible for the slow but progressive degeneration of cartilage tissue.