title: A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.
abstract: Leukocytes have been shown to play an important role in the development of isolated organ injury after experimental ischemia and reperfusion. To examine the role of leukocytes in generalized ischemia-reperfusion injury we used the MAb 60.3 (directed to the human leukocyte adherence glycoprotein, CD18) to block leukocyte adherence functions in a rabbit model of hemorrhagic shock and resuscitation. In control animals subjected to 1 h of shock (mean blood pressure 45 torr and mean cardiac output 30% of baseline) followed by resuscitation, only 29% survived 5 d. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 100% of the MAb 60.3-treated animals survived 5 d (P less than 0.01) and organ injury was absent or markedly attenuated. The control animals also had a persistent acidosis, lost more weight, and had evidence of continued gastrointestinal bleeding in contrast to MAb 60.3-treated animals. We conclude that increased leukocyte adhesiveness plays an important role in the development of multiple organ injury and death after generalized ischemia-reperfusion and that this injury may be significantly reduced by blocking leukocyte adherence functions with the MAb 60.3.
authors.affiliation: Department of Surgery, University of Washington, Seattle 98104.
authors.forename: N B
authors.initials: NB
authors.lastname: Vedder
authors.forename: R K
authors.initials: RK
authors.lastname: Winn
authors.forename: C L
authors.initials: CL
authors.lastname: Rice
authors.forename: E Y
authors.initials: EY
authors.lastname: Chi
authors.forename: K E
authors.initials: KE
authors.lastname: Arfors
authors.forename: J M
authors.initials: JM
authors.lastname: Harlan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000293:injuries; D007511:Ischemia / Q000517:prevention & control; D008099:Liver / Q000098:blood supply / Q000293:injuries; D008168:Lung / Q000098:blood supply; D055370:Lung Injury; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins / Q000276:immunology*; D011817:Rabbits; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D001798:Blood Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins