Antibody against leukocyte integrin (CD18) prevents reperfusion-induced lung vascular injury.
We studied the effects of pretreatment of rabbits with a monoclonal antibody (MoAb) IB4 directed against an epitope on the common beta-chain of leukocyte adhesion glycoprotein CD18 on the development of pulmonary edema following pulmonary artery occlusion and reperfusion. A balloon catheter occluded the right pulmonary artery in rabbits for 24 h, and the balloon was then deflated to allow reperfusion for 2 h. The lungs were removed, attached to a weighing balance, and perfused with Ringer-albumin solution (0.5 g/100 ml). IB4 (0.5 mg/kg) was infused 45 min before the start of reperfusion. In another experiment, we infused OKM-1 (0.5 mg/kg), a control MoAb directed against an irrelevant epitope on the alpha-chain of CD11b/CD18. IB4 prevented rabbit neutrophil adherence to pulmonary artery endothelial cells in vitro in response to a variety of stimuli, whereas OKM-1 was ineffective. Pulmonary artery occlusion and reperfusion increased the lung myeloperoxidase (MPO) content, whereas IB4 prevented the increase in MPO content. The increase in lung weight in the IB4-treated group (400 +/- 40 mg from baseline) was less (P less than 0.001) than in the untreated control group (1,400 +/- 90 mg) and the OKM-1-treated control group (1,320 +/- 125 mg). IB4 pretreatment also prevented the increase in pulmonary capillary filtration coefficient (a measure of capillary permeability to water) occurring in control and OKM-1-treated groups. The results indicate that neutrophil sequestration in the pulmonary microcirculation mediated by CD18 glycoprotein is a major determinant of reperfusion-induced lung vascular injury.
Horgan
M J
MJ
Department of Pediatrics, Albany Medical College of Union University, New York 12208.
Wright
S D
SD
Malik
A B
AB
D000818:Animals; D000906:Antibodies; D000954:Antigens, Surface / Q000276:immunology; D018821:CD18 Antigens; D002196:Capillaries / Q000502:physiology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D008168:Lung / Q000098:blood supply* / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000502:physiology*; D011652:Pulmonary Circulation; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
D000906:Antibodies; D000954:Antigens, Surface; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D009195:Peroxidase