VITRONECTIN EXPRESSION IN RHEUMATOID ARTHRITIC SYNOVIA - INHIBITION OF PLASMIN GENERATION BY VITRONECTIN PRODUCED IN-VITRO

The plasmin-generating system controls, to a great extent, the degree of connective tissue destruction as well as fibrin deposition-two cont ributors to the pathogenesis generated in diseases such as rheumatoid arthritis. Vitronectin, an adhesive blood glycoprotein, has the potent ial to modulate this system by its known capacity to interact with pla sminogen activator inhibitor-1, plasminogen activators, the urokinase plasminogen activator receptor, and plasminogen. The net effect of the se interactions, in terms of plasmin generation, is not known as yet. In the present study, we have investigated the possible expression and role of vitronectin in rheumatoid arthritic synovia. Analysis of syno vial frozen sections by immunofluorescence showed the presence of vitr onectin in the 13 cases studied. In situ hybridization analysis demons trated the presence of vitronectin mRNA in cells present in areas rich in infiltrating inflammatory cells. The adherent population of the rh eumatoid arthritic synovial cells was isolated and found to synthesize and secrete vitronectin into the medium (seven of 10 isolates), as as sessed by metabolic labelling and immunoprecipitation. Plasmin-generat ing activity was detected in the adherent synovial cells, and this act ivity was increased by antibodies to vitronectin. Our findings show, f or the first time, that vitronectin can be endogenously produced in a pathophysiological system where it can inhibit the generation of plasm in.