RABBIT MODELS OF ARTHRITIS - IMMUNOLOCALIZATION OF MATRIX METALLOPROTEINASES AND TISSUE INHIBITOR OF METALLOPROTEINASE IN SYNOVIUM AND CARTILAGE

The distribution of the matrix metalloproteinases, collagenase, strome lysin, gelatinases A and B, and the tissue inhibitor of metalloprotein ases in cartilage and synovium removed from rabbits up to 27 days afte r induction of two models of arthritis was investigated by immunolocal ization. Following intra-articular injection of poly-D-lysine/hyaluron ic acid coacervate, collagenase and stromelysin were found bound to ca rtilage matrix, but there was little increase in chondrocyte synthesis of these enzymes. The synovium underwent a complex wound healing resp onse involving invagination and encapsulation of the coacervate and in flammatory cell debris, during which all four metalloproteinases and t issue inhibitor of metalloproteinase could be immunolocalized. The sec ond model, intra-articular injection of ovalbumin into sensitized rabb its, caused considerable chondrocyte necrosis; collagenase was found b ound to cartilage matrix on day 13, although again there was little ev idence of synthesis by chondrocytes. Inflammatory cell infiltration of meniscoid synovia took place initially, followed by fibrosis involvin g macrophagelike cells secreting gelatinase A. In both models there wa s rapid loss of glycosaminoglycan metachromasia from the cartilage mat rix. These results are discussed in relation to current knowledge of m etalloproteinase involvement in the chronic rheumatoid synovial pannus erosion of cartilage in humans. The data suggest that there are consi derable differences between rheumatoid arthritis and these models, and their use must therefore be carefully defined.