ROLE OF COMPLEMENT IN RATS INJECTED WITH LIPOSOME-ENCAPSULATED HEMOGLOBIN

Previous studies have documented that liposome-encapsulated hemoglobin (LEH) can cause a rapid and transient thrombocytopenia following intr avenous injection into small animals. The present study evaluated the role of complement during the LEH-induced thrombocytopenia in rats. We have compared changes in platelet levels in the blood, platelet organ distribution, and total hemolytic complement levels following intrave nous administration of LEH in control and complement-depleted rats. Ch anges in platelet organ distribution at various times after LEH admini stration were monitored by labeling autologous platelets with indium-l ll (In-111)-oxine and imaging the In-111-platelets with a gamma camera after reinjection. Platelet counts were determined by light-scatterin g methods and by following In-111 radioactivity at various times after LEH administration. Platelet levels did not significantly change for the complement-depleted rats during the 60 min following an injection of LEH, whereas thrombocytopenia (40% decrease) was noted within 4 min post-LEH-injection for control rats with a gradual return to baseline circulating platelet levels within 60 min. This drop in circulating p latelets was correlated with a rapid redistribution of In-111-platelet s from the circulation to the lungs and liver, whereas complement-depl eted rats showed no transient movement of the In-111-platelets from th e circulation. Baseline complement levels of 21.6 +/- 2.2 CH50/ml for control rats and 0.2 +/- 0.1 CH50/ml for complement-depleted rats did not significantly change during the 60 min following LEH administratio n. This study suggests that complement must be present during LEH-indu ced transient thrombocytopenia, as complement-depleted rats underwent no thrombocytopenia, and that the transient LEH-induced thrombocytopen ia may be associated with complement activation. (C) 1997 Academic Pre ss.