Effect of LFA-1 beta antibody on leukocyte adherence in response to hemorrhagic shock in rats

The activation and adherence of leukocytes to the venular endothelium are c ritical steps in the pathogenesis of generalized microvascular injury follo wing hemorrhagic shock. Previous studies have shown that the integrins CD11 /CD18 play a significant role in this interaction. The purpose of this stud y is to examine the efficacy of anti-LFA-1 beta, an antibody to CD11a/CD18, in attenuating leukocyte adherence before. during, and after hemorrhagic s hock. Following a control period, blood was withdrawn to reduce the mean ar terial pressure to 40 mm Hg for 30 min in urethane-anesthetized rats. Mesen teric venules in a transilluminated segment of the small intestines were ex amined to quantitate leukocyte adherence using intravital microscopy. In sh am-operated rats (control), there was minimal to no leukocyte adherence thr oughout the experiment. Hemorrhagic shock resulted in significant leukocyte adherence during resuscitation (10.8 +/- 1.7 cells/100 mu m, P < 0.01) whe n compared to control. Anti-LFA-1 beta, when given before hemorrhagic shock , significantly attenuated leukocyte adherence during resuscitation (1.1 +/ - 0.8, P < 0.01) when compared with hemorrhagic shock alone, This protectiv e effect of anti-LFA-1 beta on leukocyte adherence was even demonstrated wh en it was given during (1.6 +/- 0.3, P < 0.01) and 10 min after hemorrhagic shock (5.8 +/- 0.4, P < 0.05). These results suggest that anti-LFA-1 beta may be of potential therapeutic benefit against microvascular injury caused by hemorrhagic shock.