A CD18 ANTIBODY PREVENTS LUNG INJURY BUT NOT HYPOTENSION AFTER INTESTINAL ISCHEMIA-REPERFUSION

Antibodies to the neutrophil CD18 integrin have been shown to ameliorate the local effects of intestinal ischemia and reperfusion (I/R). In addition to local mucosal injury, intestinal I/R results in systemic hypotension and injury to the lungs with lung leukose-questration. This study tests the effect of a CD18 monoclonal antibody on the hypotension and lung injury after intestinal I/R. In anesthetized rabbits, the superior mesenteric artery was clamped for 60 min followed by 3 h of reperfusion. Animals were treated with saline, an anti-CD18 monoclonal antibody (R15.7 MAb), or nonspecific immunoglobulin G. Another nonischemic group were sham controls. Neutrophil sequestration was assessed by measure of lung myeloperoxidase (MPO) and permeability by lung-to-blood concentration ratio of I-125-labeled bovine serum albumin and wet-to-dry weight ratio. Immediately after reperfusion, mean arterial pressure fell to 49 +/- 2.1 mmHg and remained at this level. The hypotension was unaffected by treatment with R15.7 MAb. Thirty minutes after reperfusion, the circulating white blood cell count fell to 2.91 +/- 0.53 X 10(3)/mm3 vs. sham 6.40 +/- 0.66 X 10(3)/mm3 (P < 0.05). Treatment with R15.7 MAb prevented this fall in white blood cell count (5.75 +/- 1.59 X 10(3)/mm). At 3 h of reperfusion in saline-treated animals there was increased MPO, 74.8 +/- 4.9 U/g vs. 42.0 +/- 4.8 U/g in sham animals (P < 0.05). Lung permeability also increased, as evidence by lung-to-blood I-125 ratio of 0.401 +/- 0.028 vs. sham ratio of 0.196 +/- 0.030 (P < 0.05) and increased lung wet-to-dry weight ratio 6.60 +/- 0.36 vs. 5.58 +/- 0.05 (P < 0.05). Treatment with R15.7 MAb reduced MPO to 49.7 +/- 7.3 U/g and completely prevented the increased lung permeability indicated by lung-to-blood I-125 0.203 +/- 0.024 and lung wet-to-dry weight ratio 5.24 +/- 0.09 (both P < 0.05). These data indicate that an MAb to the neutrophil CD18 integrin prevents lung injury but not hypotension after intestinal I/R.