STUDIES ON THE EFFECT OF PENTOSAN POLYSULFATE ON PROTEOGLYCAN DEGRADATION BY LEUKOCYTE NEUTRAL PROTEASES

Pentosan polysulfate (SP-54), an anti-inflammatory agent, inhibits the degradation of proteoglycan by a human leukocyte neutral protease preparation enriched with elastase. Under the assay conditions used, a 50% inhibition is seen at .apprx. 3.5 .times. 10-8 M SP-54. SP-54, at concentrations up to 1 .times. 10-5 M, does not affect the proteolytic degradation of proteoglycan catalyzed by trypsin, chymotrypsin and pancreatic elastase. The inhibitory effect of SP-54 is most probably related to the interaction of the drug with the proteoglycan substrate. The resulting complex is stable to proteolytic degradation by leukocyte neutral proteases. This complex is readily dissociated by 0.5 M NaCl and the resulting proteoglycan can be subsequently degraded by the leukocyte protease preparation.