The effect of anti-L-selectin (EL-246) on remote lung injury after infrarenal ischemia/reperfusion

The clinical concern in using neutrophil adhesion blocking agents is whether or not neutrophil function may be down-regulated, rendering neutrophils incapable of dealing with infections that may threaten the patient. In a sheep model of ischemia and reperfusion, we have investigated the effect of anti-L-selectin (EL-246) on the pulmonary injury as well as on the neutrophil function, assessed by in vitro chemiluminescence (CL) of isolated neutrophils. Infrarenal ischemia (3 h) followed by reperfusion (4 h) resulted in pulmonary capillary leakage as evident by an increased alveolar/plasma protein ratio (.76 vs. .19 in control, p < .01) and also led to a significant pulmonary neutrophil accumulation as assessed by the myeloperoxidase content in homogenized lung tissue (31.7 vs. 6.1 U, p < .01). Anti-L-selectin, infused at a dose of 1 mg/kg at the time of reperfusion, significantly reduced the pulmonary leakage by 59% (.42 vs. .76 U) and neutrophil accumulation by 84% (10.2 vs. 31.7 U). Pulmonary function improved by anti-L-selectin as represented by an increase of the arterio-venous oxygen ratio. CL decreased from 1.85 x 10(5) counts(c)/min to 1.02 x 10(6) c/min at 15 min of reperfusion in the positive control followed by a subsequent return to normal. In contrast to myeloperoxidase, the significant change in CL was not affected by the use of anti-L-selectin. Based on our data, we conclude that anti-L-selectin is able to significantly reduce the pulmonary injury in ischemia-reperfusion but in parallel does not result in neutrophil dysfunction regarding for example, the respiratory burst. Thus, using neutrophil adhesion blocking agents in patients appears to be unlikely to increase the risk of septic complications.