Anti-heparin activity of lysosomal cationic proteins from polymorphonuclear leukocytes.

C ATIONIC PROTEINS are important constituents of polymorphonuclear ( PMN ) leukocyte lysosomes. These proteins are rich in arginine and lysine. This accounts for their strong electro-positivity.13 These proteins are without apparent enzyme activity; nevertheless they possess a variety of biological activities.1’4#{176} We have recently described an anticoagulant activity of these proteins that is probably related to their electro-positive charge.7 The lysosomal cationic proteins ( LCP) appear to interfere with the role of negatively charged phospholipid micelles, or possibly platelet membranes, in the reactions involving Factor V ( proaccelerin), Factor X (Stuart factor) and calcium.7 Thus, they inhibit clotting by a mechanism different from that of heparin.8’9 In view of previous reports that crude extracts of leukocytes have an antiheparin effect,10’11 and the known anti-heparin action of various other cationic substances like protamine,’2’13 synthetic polylysine14”5 and polybrene,16 this study was undertaken to determine if PMN lysosomal cationic proteins also possess anti-heparin activity. Our results show that LCP from polymorphonuclear leukocytes do inhibit heparin but lose their own anticoagulant effect in the process. Further, an apparent inhibition of antithrombin III by LCP is most likely the result of a clot-promoting effect of LCP on fibrinogen or the reactions leading to fibrin formation.