Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion.
The role of P-selectin in leukocyte-endothelial interaction after splanchnic arterial occlusion and reperfusion (SAO/R) in pentobarbital-anesthetized rats was investigated employing a P-selectin-neutralizing monoclonal antibody (i.e., MAb PB1.3). MAb PB1.3 (1 mg/kg) given intravenously to SAO/R rats just before reperfusion significantly attenuated leukocyte rolling and adherence in mesenteric postcapillary venules as observed via intravital microscopy. Likewise, ileal myeloperoxidase (MPO) activity was decreased from 4.6 +/- 0.6 in nontreated ischemic rats to 2.0 +/- 0.2 U/100 mg (P < 0.01), indicating a lesser degree of polymorphonuclear leukocyte (PMN) accumulation. A significantly lower plasma free amino-nitrogen concentration was observed in MAb PB1.3-treated rats vs. untreated (P < 0.01), suggesting decreased tissue injury after reperfusion. Immunohistochemical localization demonstrated significant expression of P-selectin in endothelial cells lining ileal postcapillary venules 30 min after reperfusion of the ischemic splanchnic circulation. Thus P-selectin appears to plays an important role in leukocyte accumulation after splanchnic ischemia-reperfusion, and the MAb PB1.3 attenuates the accumulation of PMNs in the ischemic-reperfused small bowel, resulting in reduced tissue injury.
Davenpeck
K L
KL
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Gauthier
T W
TW
Albertine
K H
KH
Lefer
A M
AM
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics; D007150:Immunohistochemistry; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008833:Microcirculation; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D013152:Splanchnic Circulation
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins