Effect of LFA-1beta 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-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 Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 min in urethane-anesthetized rats.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.
Department of Surgery, University of Kansas, Medical Center, Kansas City 66160, USA.
E W
EW
Childs
D M
DM
Smalley
M
M
Moncure
J L
JL
Miller
L Y
LY
Cheung
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000473:pathology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008297:Male; D008833:Microcirculation; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D014699:Venules
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion