A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.
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.
Vedder
N B
NB
Department of Surgery, University of Washington, Seattle 98104.
Winn
R K
RK
Rice
C L
CL
Chi
E Y
EY
Arfors
K E
KE
Harlan
J M
JM
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*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D001798:Blood Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins