Effect of LFA-1beta antibody on leukocyte adherence in response to hemorrhagic shock in rats.
Effect of LFA-1beta antibody on leukocyte adherence in response to hemorrhagic shock in rats.
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发表时间：
2000
期刊：
影响因子：
3.1
通讯作者：
E. Childs;D. Smalley;M. Moncure;J. Miller;L. Cheung
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文献类型：
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作者：
E. Childs;D. Smalley;M. Moncure;J. Miller;L. Cheung
白细胞的活化和粘附是失血性休克后全身性微血管损伤的发病机制中的关键步骤。以往的研究表明，整合素CD 11/CD 18在这种相互作用中起着重要作用。本研究的目的是检测抗LFA-1 β（一种CD 11 a/CD 18抗体）在失血性休克前、中、后减弱白细胞粘附的疗效。在对照期后，在麻醉大鼠中抽取血液以将平均动脉压降低至40 mm Hg持续30 min。使用活体显微镜检查小肠透照段中的肠系膜小静脉以定量白细胞粘附。在假手术大鼠（对照组）中，整个实验过程中白细胞粘附极少或无。与对照组相比，失血性休克在复苏期间导致显著的白细胞粘附（10.8 +/-1.7个细胞/100 μ m，P < 0.01）。与单纯失血性休克相比，在失血性休克前给予抗LFA-1 β抗体可显著降低复苏过程中的白细胞粘附（1.1 ± 0.8，P < 0.01）。抗LFA-1 β对白细胞粘附的保护作用甚至在失血性休克后10分钟（1.6 ± 0.3，P < 0.01）和10分钟（5.8 ± 0.4，P < 0.05）给予时也得到了证实。这些结果表明，抗LFA-1 β可能对失血性休克引起的微血管损伤具有潜在的治疗益处。
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-1beta, 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 Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 min in urethane-anesthetized rats.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 microm, P < 0.01) when compared to control. Anti-LFA-1beta, 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-1beta 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-1beta may be of potential therapeutic benefit against microvascular injury caused by hemorrhagic shock.