In vitro and in vivo modulation of vascular barrier integrity by sphingosine 1-phosphate: mechanistic insights.
Sphingosine 1-phosphate (S1P), a biologically active lipid growth factor, induces robust endothelial cell activation resulting in cellular locomotion, vascular maturation and angiogenesis. Recent work by our laboratory has demonstrated S1P to enhance the cellular barrier function of the vascular endothelium. S1P-induced modulation of vascular permeability is effected through profound cytoskeletal reorganization initiated by cell surface receptor-mediated G protein activation and downstream signaling via the Rho family of small GTPases. The details of the downstream signaling mechanism remain an active area of in vitro investigation. Translational investigation suggests a profound impact of S1P administration in the modulation of edema formation in disease state manifest as acute inflammatory lung injury in which increased vascular permeability is a hallmark feature. These data support an exciting potential therapeutic role for S1P in vascular barrier enhancement necessary for the treatment of critically ill patients.
McVerry
Bryan J
BJ
Center for Translational Respiratory Medicine, Johns Hopkins University School of Medicine, Division of Pulmonary and Critical Care Medicine, 1830 E. Monument Street Room 527, Baltimore, MD 21287, USA.
Garcia
Joe G N
JG
D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D008954:Models, Biological; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D020744:rac GTP-Binding Proteins / Q000502:physiology
D043925:Angiogenesis Inducing Agents; D000893:Anti-Inflammatory Agents; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D020744:rac GTP-Binding Proteins; D013110:Sphingosine