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

The activation and adherence of leukocytes to the venular endothelium are critical steps in the pathogenesis of generalized microvascular injury following hemorrhagic shock. Previous studies have shown that the integrins CD11/CD18 play a significant role in this interaction. The purpose of this study is to examine the efficacy of anti-LFA-1 beta, an antibody to CD11a/CD18, in attenuating leukocyte adherence before. during, and after hemorrhagic shock. Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 min in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small intestines were examined to quantitate leukocyte adherence using intravital microscopy. In sham-operated rats (control), there was minimal to no leukocyte adherence throughout the experiment. Hemorrhagic shock resulted in significant leukocyte adherence during resuscitation (10.8 +/- 1.7 cells/100 mu m, P < 0.01) when 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 protective effect of anti-LFA-1 beta on leukocyte adherence was even demonstrated when 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.