Sphingosylphosphorylcholine induces endothelial cell migration and morphogenesis

Sphingosylphosphorylcholine (SPC) is one of the biologically active phospho lipids that may act as extracellular messengers. Particularly important is the role of these lipids in the angiogenic response, a complex process invo lving endothelial cell migration, proliferation, and morphologic differenti ation. Here we demonstrate that SPC and its hydrolytic product, sphingosine , induce chemotactic migration of human and bovine endothelial cells. The r esponse is approximately equal to that elicited by vascular endothelial cel l growth factor. The effect of SPC and sphingosine was associated with a ra pid down-regulation of Edg1, a sphingosine 1-phosphate (SPP)-specific recep tor involved in endothelial cell chemotaxis. Both SPC and sphingosine induc ed differentiation of endothelial cells into capillary-like structures in v itro. Thus, SPC and sphingosine join SPP among the biologically active lipi ds with angiogenic potential. Since neuronal abnormalities accompany pathol ogical accumulation of SPC in brain tissue, it is possible that SPC is a mo dulator of angiogenesis in neural tissue upon its release from brain cells following trauma or neoplastic growth. (C) 2000 Academic Press.