Hemorrhagic shock induced up-regulation of P-selectin expression is mediated by factors in mesenteric lymph and blunted by mesenteric lymph duct interruption.
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.
Adams
C A
CA
Department of Surgery, UMD-New Jersey Medical School, Newark, New Jersey 07103, USA.
Sambol
J T
JT
Xu
D Z
DZ
Lu
Q
Q
Granger
D N
DN
Deitch
E A
EA
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
D019007:P-Selectin