Wickel D J, Mercer-Jones M, Peyton J C, Shrotri M S, Cheadle W G
Department of Surgery, University of Louisville School of Medicine and the Veterans Affairs Medical Center, Kentucky 40292, USA.
Shock. 1998 Oct;10(4):265-9. doi: 10.1097/00024382-199810000-00006.
Neutrophil (PMN) influx into the peritoneal cavity in response to bacterial peritonitis is an indispensable aspect of host defense. PMNs also are responsible for the remote organ injury observed after major abdominal infection. The aim of this study was to examine the effect of selectin blockade on PMN migration into the peritoneum and on PMN sequestration in the lungs, early in the course of peritonitis. Cecal ligation and puncture (CLP) was performed on P-selectin-deficient (P-def) mice and their genetic controls (C57). Both groups were treated with anti-E-selectin antibody, anti-L-selectin, or isotypic control immunoglobulin G at the time of CLP. 6 h after CLP, mice were sacrificed. Peritoneal PMN migration decreased in P-def mice compared with C57 controls after CLP. Blockade of E- or L-selectin alone in controls did not alter peritoneal PMN influx or circulating PMNs after CLP. In the P-def mice, treatment with anti-E-antibody or anti-L-antibody nearly eliminated PMN influx into the peritoneum. In contrast, circulating PMNs markedly increased after CLP in P-def mice when compared with baseline values. Lung myeloperoxidase increased in all groups of mice following CLP. Blockade of P-selectin with anti-P-selectin antibody elicited a response similar to that observed in the P-def mice. In conclusion, P-selectin mediates PMN influx into the peritoneal cavity, while E- and L-selectins do not appear to play any significant role in the 6 h time period following CLP. Lung PMN sequestration, after CLP, occurred independent of P-, E-, or L-selectin expression. Blockade of P-selectin during peritonitis appears to be potentially deleterious by preventing early PMN influx into the compartment containing the septic focus.
中性粒细胞（PMN）因细菌性腹膜炎而流入腹腔是宿主防御的一个不可或缺的方面。PMN也与严重腹部感染后观察到的远隔器官损伤有关。本研究的目的是在腹膜炎病程早期，研究选择素阻断对PMN向腹膜迁移以及在肺中滞留的影响。对P-选择素缺陷（P-def）小鼠及其基因对照（C57）进行盲肠结扎和穿刺（CLP）。两组在CLP时均用抗E-选择素抗体、抗L-选择素或同型对照免疫球蛋白G进行治疗。CLP后6小时，处死小鼠。与CLP后的C57对照相比，P-def小鼠的腹膜PMN迁移减少。单独阻断对照中的E-或L-选择素不会改变CLP后的腹膜PMN流入或循环PMN。在P-def小鼠中，用抗E-抗体或抗L-抗体治疗几乎消除了PMN向腹膜的流入。相反，与基线值相比，P-def小鼠CLP后循环PMN显著增加。CLP后所有小鼠组的肺髓过氧化物酶均增加。用抗P-选择素抗体阻断P-选择素引发的反应与在P-def小鼠中观察到的相似。总之，P-选择素介导PMN流入腹腔，而E-和L-选择素在CLP后的6小时时间段内似乎未发挥任何重要作用。CLP后肺中PMN的滞留与P-、E-或L-选择素的表达无关。在腹膜炎期间阻断P-选择素可能会因阻止PMN早期流入含有感染灶的腔室而具有潜在危害。
