Platelet lipid(s) bound to albumin increases endothelial electrical resistance: mimicked by LPA

The objectives were to determine whether the permeability-decreasing activi ty of platelet-conditioned medium (PCM) is associated with a lipid bound to albumin and whether lysophosphatidic acid (LPA) is present in the PCM. A d ecrease in permeability was assessed by an increase in electrical resistanc e across endothelial cell monolayers derived from bovine pulmonary arteries and microvessels. The Sephacryl S-200 fraction of PCM that contained album in, the albumin immunoprecipitate from the PCM, and the methanol extract fr om the albumin immunoprecipitate all increased endothelial electrical resis tance. Increased electrical resistance induced by PCM was not abolished by boiling and was mimicked by 1-oleoyl-LPA and 1-palmitoyl-LPA. Analysis of a methanol-chloroform extract of one sample of PCM by electrospray mass spec trometry revealed many fatty acids, ceramide, diacylglycerol, phosphatidic acid, and palmitoyl-LPA, but analysis of a second sample of PCM and the met hanol extract of its albumin immunoprecipitate revealed no LPA, only lipids . These findings indicate that a bioactive lipid(s), possibly LPA, released from platelets and subsequently bound to albumin forms an active complex t hat decreases endothelial permeability.