title: Microvascular thrombosis and CD40/CD40L signaling.
abstract: BACKGROUND
  Although inflammation and thrombosis are now recognized to be interdependent processes that activate and perpetuate each other, the signaling molecules that link these two processes remain poorly understood.
  
  
  OBJECTIVE
  The objective of this study was to assess the contribution of the CD40/CD40L signaling system to the enhanced microvascular thrombosis that accompanies two distinct experimental models of inflammation, that is, endotoxemia (lipopolysaccharide [LPS]) and dextran sodium sulfate (DSS)-induced colitis.
  
  
  METHODS
  Thrombosis was induced in cerebral (LPS model) and cremaster muscle (DSS model) arterioles and venules of wild-type (WT) mice and mice deficient in either CD40 (CD40(-/-)) or CD40L (CD40L(-/-)), using the light/dye (photoactivation) method.
  
  
  CONCLUSIONS
  A comparison of thrombus formation between WT and mutant mice revealed a role for CD40 and/or CD40L in the inflammation-enhanced thrombosis responses in both of the cerebral and muscle vasculatures. However, the relative contributions of CD40 and its ligand to thrombus formation differed between vascular beds (brain vs. muscle) and vessel types (arterioles vs. venules). The protective effect of CD40L deficiency in cerebral arterioles exposed to LPS was significantly blunted by administration of soluble CD40L. These findings implicate CD40 and its ligand in the enhanced thrombus formation that is associated with acute and chronic inflammation.
authors.affiliation: Wolfson Neuroscience Laboratories, Faculty of Medicine, Imperial College, London, UK. f.gavins@imperial.ac.uk
authors.forename: F N E
authors.initials: FN
authors.lastname: Gavins
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Russell
authors.forename: M
authors.initials: M
authors.lastname: Perretti
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000209:etiology; D003092:Colitis / Q000150:complications; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D007249:Inflammation / Q000150:complications; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055806:Microvessels; D018482:Muscle, Skeletal / Q000098:blood supply; D015398:Signal Transduction; D013927:Thrombosis / Q000209:etiology*
chemical_list: D019013:CD40 Antigens; D008070:Lipopolysaccharides; D023201:CD40 Ligand; D016264:Dextran Sulfate