INHIBITION OF TYPE-I AND TYPE-II PHOSPHOLIPASE A(2) BY PHOSPHATIDYL-ETHANOLAMINE LINKED TO POLYMERIC CARRIERS

We have previously shown that cell surface proteoglycans protect the c ell membrane from the action of extracellular phospholipase A(2) (PLA( 2)) enzymes [Dan, P., Nitzan, D. W., Dagan, A., Ginsburg, I., and Yedg ar, S. (1996) FEES Lett. 383, 75-78]. Cell-impermeable PLA(2) inhibito rs (ExPLIs) were prepared by linking phosphatidylethanolamine (PE) to polymeric carriers, specifically, carboxymethyl cellulose, heparin, or hyaluronic acid. The structure of these inhibitors enables the incorp oration of their PE moiety into the membrane while the polymer remains at the membrane surface. In the present study, we show that the ExPLI s are effective inhibitors of the hydrolysis of different phospholipid s in biological (Escherichia coli) and model (phospholipid vesicle) me mbranes, by diverse types of PLA(2) enzymes, specifically human recomb inant synovial fluid and C. atrox (type II), as well as Naja mocambiqu e and porcine pancreatic (type I) PLA(2). It is proposed that the exte rnal polymers of the ExPLIs, which are anchored to the membrane by the PE, mimic the naturally occurring cell surface proteoglycans and simi larly protect membranes from the action of exogenous PLA(2).