Sphingosylphosphorylcholine induces endothelial cell migration and morphogenesis.
Sphingosylphosphorylcholine (SPC) is one of the biologically active phospholipids that may act as extracellular messengers. Particularly important is the role of these lipids in the angiogenic response, a complex process involving endothelial cell migration, proliferation, and morphologic differentiation. Here we demonstrate that SPC and its hydrolytic product, sphingosine, induce chemotactic migration of human and bovine endothelial cells. The response is approximately equal to that elicited by vascular endothelial cell growth factor. The effect of SPC and sphingosine was associated with a rapid down-regulation of Edg1, a sphingosine 1-phosphate (SPP)-specific receptor involved in endothelial cell chemotaxis. Both SPC and sphingosine induced differentiation of endothelial cells into capillary-like structures in vitro. Thus, SPC and sphingosine join SPP among the biologically active lipids with angiogenic potential. Since neuronal abnormalities accompany pathological accumulation of SPC in brain tissue, it is possible that SPC is a modulator of angiogenesis in neural tissue upon its release from brain cells following trauma or neoplastic growth.
Boguslawski
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G
Experimental Cell Research Program, Clarian Health Partners, Inc., Indianapolis, Indiana 46202, USA.
Lyons
D
D
Harvey
K A
KA
Kovala
A T
AT
English
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D
D000818:Animals; D001011:Aorta; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D008222:Lymphokines / Q000494:pharmacology; D008246:Lysophospholipids; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014470:Umbilical Cord; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D016228:Endothelial Growth Factors; D017874:Immediate-Early Proteins; D008222:Lymphokines; D008246:Lysophospholipids; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010566:Virulence Factors, Bordetella; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C060506:sphingosine 1-phosphate; D013498:Suramin; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D020741:rho GTP-Binding Proteins; D013110:Sphingosine