The binding of phosphatidylglycerol liposomes to rat platelets is mediated by complement

Summary Previous work has shown that intravenous administration of phosphatidylglycercol (PG) containing liposomes to rats results in a rapid transient decline in platelet count (1). Here the interactions of PG liposomes with rat platelets in vitro have been examined with the aim of characterizing factors associated with the decline. It is shown that PG liposomes induce formation of rat (but not human) platelet-liposome microaggregates in vitro. The PC liposome dependent thrombocytopenia observed in vivo can therefore be attributed to sequestration of PG liposome-platelet aggregates. Further, the aggregation of platelets with PG liposomes, which can be monitored as a reduction in platelet count using a coulter counter, is shown to be mediated by a serum complement factor, likely C3b. This is indicated by a requirement of plasma for the in vitro reduction in platelet count induced by PG liposomes, and the inhibition of this effect by heat treatment of plasma, by incubation of plasma with purified cobr a venom factor, or by removal of C3 from plasma. lntrbduction Recent work from this laboratory has shown that intravenous injectio nof negatively charged liposomes induces a transient thrombocytopenia in rodents (1,2). This effect is most striking for liposom epreparations containing the negatively charged lipid phosphatidylglycerol (PG). The transient reduction in platelet counts is associated with sequestration of platelets and liposomes in the liver and lung (2). This indicates a potential role of platelets i nthe removal of liposomes from the circulation following intravenous injection, Preliminary investigations suggest that the transien t thrombocytopenia results from a transient liposome-platelet interaction (1). The nature of this interaction is clearly of interest. In this regard ,it has been well documented that liposomes bind a variety of serum components (3). Specifically, negatively charged PG containing liposomes bind significantly more serum proteins than neutral liposomes. These serum components may play a role in binding of liposomes to platelets.