title: Hemorrhagic shock induced up-regulation of P-selectin expression is mediated by factors in mesenteric lymph and blunted by mesenteric lymph duct interruption.
abstract: BACKGROUND
  Previous studies have shown that mesenteric lymph duct interruption prevents lung injury and decreases lung neutrophil sequestration after hemorrhagic shock (HS). Since endothelial cells rapidly express P-selectin after ischemia/reperfusion injury and HS-induced lung injury appears to involve neutrophil-endothelial cell interactions, we tested the following two hypotheses. First, that HS increases endothelial cell P-selectin expression and that interruption of mesenteric lymph flow in vivo would diminish this expression. Second, that incubation of human umbilical vein endothelial cells with post-HS mesenteric lymph but not sham shock (SS) lymph or postshock portal vein plasma would up-regulate P-selectin expression.
  
  
  METHODS
  Pulmonary microvascular P-selectin expression was measured in male rats subjected to 90 minutes of HS (30 mm Hg), SS, or HS with lymphatic ligation, with a dual radiolabeled monoclonal antibody technique. The lungs from these animals were subsequently harvested and P-selectin expression was expressed as mean +/- SEM nanograms of monoclonal antibody per gram of tissue.
  
  
  RESULTS
  Pulmonary P-selectin expression was 2.0 +/- 0.4 after SS, 9.7 +/- 3.0 after HS, but decreased to 2.3 +/- 0.3 after HS with lymph interruption (p < 0.05 HS vs. SS or HS plus lymph ligation). Incubation of human umbilical vein endothelial cells with shock lymph collected 3 to 4 hours after shock resulted in a nearly fivefold increase in P-selectin expression (p < 0.001) as compared with SS lymph, lymph collected 6 hours after shock, or postshock portal vein plasma.
  
  
  CONCLUSIONS
  These results support the concept that gut-derived lymph promotes HS-induced lung injury through up-regulation of microvascular adhesion molecules and that intestinal lymph duct interruption may prevent distant organ injury by blunting the expression of these molecules.
authors.affiliation: Department of Surgery, UMD-New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Adams
authors.forename: J T
authors.initials: JT
authors.lastname: Sambol
authors.forename: D Z
authors.initials: DZ
authors.lastname: Xu
authors.forename: Q
authors.initials: Q
authors.lastname: Lu
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
authors.forename: E A
authors.initials: EA
authors.lastname: Deitch
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D066298:In Vitro Techniques; D008026:Ligation; D008196:Lymph / Q000502:physiology; D008208:Lymphatic System / Q000601:surgery*; D008297:Male; D008643:Mesentery; D019007:P-Selectin / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000517:prevention & control; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology* / Q000601:surgery*; D018709:Statistics, Nonparametric; D015854:Up-Regulation
chemical_list: D019007:P-Selectin