Pulmonary microvascular injury after intestinal ischemia-reperfusion: role of P-selectin.
The objective of this study was to determine whether pulmonary endothelial expression of the adhesive glycoprotein P-selectin contributes to the lung injury and leukostasis observed after intestinal ischemia-reperfusion (I/R). The pulmonary capillary filtration coefficient and lung myeloperoxidase activity were determined in rat lungs isolated after 120 min of superior mesenteric artery occlusion and 90 min of reperfusion. Intestinal I/R resulted in a marked increase in the pulmonary capillary filtration coefficient compared with control and sham-operated rats. The increase in pulmonary microvascular permeability elicited by intestinal I/R was effectively prevented by pretreatment with a P-selectin monoclonal antibody (MAb; MAb PB1.3) but was unaffected by a control MAb. The intestinal I/R-induced increase in pulmonary microvascular permeability was accompanied by a dramatic sequestration of granulocytes in the lung compared with control and sham-operated rats; however, neither the P-selectin nor the control MAbs affected this event. These results indicate that P-selectin contributes to the pulmonary microvascular dysfunction observed after intestinal I/R. The inhibition of intestinal I/R-induced lung injury by immunoneutralization of P-selectin appears to be unrelated to the accompanying lung leukosequestration.
Carden
D L
DL
Department of Physiology and Biophysics, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Young
J A
JA
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D007958:Leukocyte Count; D008171:Lung Diseases / Q000503:physiopathology*; D008297:Male; D009929:Organ Size; D019007:P-Selectin; D009195:Peroxidase / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D009195:Peroxidase