Effects of differently composed liposomes on pulmonary arterial pressure in sheep--involvement of pulmonary intravascular macrophages

Abstract

The authors previously reported that liposomes, when injected intravenously, produce transitory pulmonary hypertension with increased secretions of thromboxane A2 from activated intravascular macrophages that phagocytize liposomes in sheep. In the present study, we attempted to determine whether such responses were modified by the lipid compositions of the liposomes. Five different types of liposomes were prepared by reverse-phase evaporation. The liposomes used were composed of phosphatidylcholine (PC), cholesterol (CHOL), and either phosphatidylglycerol (PG-liposomes), phosphatidylserine (PS-liposomes), phosphatidylethanolamine (PE-liposomes), stearlyamine (SA-liposomes) or none (PC-liposomes). The net charges of PG and PS-liposomes were negative, SA-liposomes were positive, PE- and PC-liposomes were neutral. Each liposome was injected intravenously to obtain a pulmonary arterial pressure response. Arterial blood was sampled before and after liposome injections to measure thromboxane B2 concentrations. All liposomes, but not PC-liposomes, produced pulmonary arterial hypertension associated with increased arterial thromboxane B2 concentrations, irrespective of the net surface charge of the liposome. PG and PS-liposomes, both of which were negatively charged, showed different dose-response curves, the two different types of neutral liposomes showed different responses, and PC-liposomes produced a small increase in pulmonary arterial pressure. PE-liposomes produced marked increases in the pulmonary arterial pressure. From these results, the authors concluded that pulmonary arterial pressure responses to the liposomes are modified by the lipid compositions of the liposomes, and that this is not caused by the difference in the net charge of each liposome.