title: Selectins influence thrombosis in a mouse model of experimental deep venous thrombosis.
abstract: BACKGROUND
  This study characterizes venous thrombosis in the mouse and examines the important role that the adhesion molecules P-selectin and E-selectin and the anti-inflammatory cytokine interleukin-10 (IL-10) play in the thrombotic process.
  
  
  METHODS
  C57BL/6 (wild-type) mice in a natural history protocol (Phase I) and gene-targeted (KO) mice for P-selectin, E-selectin, P/E-selectin, and IL-10 in a follow-up protocol (Phase II) were studied. Inferior vena caval thrombosis was produced by ligation just below the renal veins, and mice were sacrificed and evaluated at various time points up to 12 days later.
  
  
  RESULTS
  Phase I: A significant increase in neutrophils on day 2 and in monocytes on day 6 postthrombosis was found in ligated vs sham animals. An associated significant increase in vein wall P-selectin mRNA (6 h, day 2) and an increase in protein (6 h through day 6) were found, while E-selectin mRNA was significantly increased (day 2 through day 6), with a smaller increase in E-selectin protein. IL-10 mRNA increased significantly later (day 2 through day 9), with the values increasing progressively. A positive correlation existed (r = 0.77) between neutrophils and thrombosis at day 2.
  
  
  METHODS
  The E-selectin and P/E-selectin double-KO mice showed the least thrombus at day 2 vs wild-type clotted mice, P < 0.01. Additionally, P/E-KO mice demonstrated the lowest inflammatory cell extravasation into the vein wall at day 2.
  
  
  CONCLUSIONS
  This study demonstrates an acute to chronic inflammatory response in the vein wall associated with venous thrombosis. Inhibition of selectins decreased thrombus formation.
authors.affiliation: Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, 48109, USA. ddmyers@umich.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Myers
authors.forename: Diana
authors.initials: D
authors.lastname: Farris
authors.forename: Angela
authors.initials: A
authors.lastname: Hawley
authors.forename: Shirley
authors.initials: S
authors.lastname: Wrobleski
authors.forename: Amy
authors.initials: A
authors.lastname: Chapman
authors.forename: Lloyd
authors.initials: L
authors.lastname: Stoolman
authors.forename: Randy
authors.initials: R
authors.lastname: Knibbs
authors.forename: Robert
authors.initials: R
authors.lastname: Strieter
authors.forename: Thomas
authors.initials: T
authors.lastname: Wakefield
mesh_terms: D000818:Animals; D002908:Chronic Disease; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D007700:Kinetics; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D013194:Staining and Labeling; D014657:Vasculitis / Q000209:etiology / Q000473:pathology; D020246:Venous Thrombosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D019040:E-Selectin; D019007:P-Selectin; D016753:Interleukin-10