THE SERINE PROTEINASE-INHIBITOR ANTILEUKOPROTEINASE SPECIFICALLY ACCUMULATES IN NORMAL BUT NOT IN ARTHRITIC CARTILAGE

Objective, To investigate whether the serine proteinase inhibitor anti leukoproteinase (aLP) specifically accumulates in articular and extraa rticular cartilage in normal and arthritic rats after intravenous (iv) injection. Methods, [I-123] Or [I-125] radiolabeled aLP acid a contro l protein of comparable size were injected iv into normal rats or rats with chronic, antigen induced arthritis (AIA). Joint accumulation of the 2 proteins was followed by scintigraphy and organ tissue radioacti vity was assessed by autoradiography and well counter measurements. Im munoprecipitation of aLP from articular cartilage was also performed a nd the content of charged molecules in normal and arthritic cartilage determined using toluidine blue staining. Results. The accumulation of both radiolabeled aLP and control protein in the normal joint was cle arly detectable by scintigraphy, with significant differences between the 2 proteins. In accordance with the scintigraphic data, direct tiss ue radioactivity measurements, immunoprecipitation, and autoradiograph y showed highly specific accumulation of radiolabeled aLP in articular and extraarticular cartilage of normal rats. The specific accumulatio n of aLP in articular cartilage was lost in rats with AIA in parallel with a loss of charged matrix molecules, Conclusion. iv injected serin e protease inhibitor aLP specifically accumulates in articular and ext raarticular cartilage of normal rats. This physiological pathway of ca rtilage accumulation, lost in proteoglycan depleted arthritic cartilag e, may serve to maintain the local balance between proteinase function and inhibition.