Activated Leukocyte-Endothelium Interactions during Ischemia Cause Endothelial Dysfunction on Reperfusion.

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Background. Injury due to reperfusion of ischemic heart or lung is mediated by leukocyte-endothelial cell interactions, dependent on the integrin CDl1b, CDl8, and its endothelial cell ligand intercellular adhesion molecule. We studied these interactions and tried to mitigate this injury with monoclonal antibodies directed against the integrins.Methods. The damage to endothelial cells exposed to ischemia and reperfusion was estimated by assessing the maximum relaxation rate of rat aortic or human pulmonary artery smooth muscle induced by endothelium-derived relaxing factor in the following groups. Group Ia : control. Group IIa : bovine leukocytes activated by PMA incubated with hypoxic bovine aortic endothelial cells (BEC). Group IIIa : bovine leikocytes activated by PMA which received monoclonal antibodies (MoAb) against CDl1b incubated with BEC.Group IVa : bovine leikocytes activated by PMA which received monoclonal antibodies (MoAb) against CDl8 incubated with BEC.Human pulmonary artery smooth muscle, human pulmonary artery endothelial cells in group Ib, IIb, IIIb, and IVb under similar conditions.Results. The maximum relaxation rate of bovine smooth muscle was 51.5<plus-minus>2.4% in group Ia. The rates in groups IIIa and IVa (24.1<plus-minus>3.7% and 20.8<plus-minus>2.5%) were significantly greater than in group IIa (8.9<plus-minus>1.3%, p<0.05). Futhermore, the maximum relaxation rate of human smooth muscle was 50.3<plus-minus>2.0% in group Ib. The rates in groups IIIb and IVb (40.9<plus-minus>1.0% and 41.8<plus-minus>1.7%) were significantly greater than in group IIb (19.7<plus-minusConclusions. Antibodies against CDl1b and CDl8 prevent reperfusion-induced lung injury mediated by neutrophil-endothelial cell interactions.