Connall T P, Zhang J, Vaziri N D, Schwartz R J, Kaupke C J, Oveisi F, Wilson S E
Department of Surgery, University of California-Irvine.
Arch Surg. 1994 Nov;129(11):1153-8. doi: 10.1001/archsurg.1994.01420350051005.
To test the hypothesis that pretreatment with radiodetoxified endotoxin (RDE) may mitigate the deleterious effects of subsequent infection, in part by modifying leukocyte adhesion receptor expression, and to investigate the cellular mechanisms of endotoxin tolerance induced by RDE.
To assess the effect of RDE pretreatment on mortality from bacterial peritonitis, rats were implanted with an intraperitoneal, barium-fecal inoculum at intervals of 0, 1, 3, and 5 days after RDE injection. Experiments were then conducted to test the effect on leukocyte adhesion receptor expression. Two groups of mice received saline solution, and one group, RDE. After 72 hours, one group received saline solution (saline/saline group), the others, lipopolysaccharide (LPS) (saline/LPS and RDE/LPS groups). Peripheral leukocytes were obtained 1 hour after injection and were analyzed for CD11b and CD18 expression by flow cytometry.
Laboratory animal study.
Survival rates were not improved in rats that were pretreated with RDE 0 and 24 hours before inoculum (0% and 7%, respectively). In rats that were pretreated 72 hours and 120 hours before inoculum, 47% (P < .01) and 60% (P < .01) survived, respectively. CD18 expression on polymorphonuclear leukocytes increased twofold in the RDE/LPS (mean +/- SEM, 300.3 +/- 32.9) and the saline/LPS (mean +/- SEM, 360.4 +/- 59.9) groups compared with controls (mean +/- SEM, 176.4 +/- 18.9) (P < .05). CD11b expression on polymorphonuclear leukocytes increased threefold in the RDE/LPS (mean +/- SEM, 91.3 +/- 8.1) and the saline/LPS (mean +/- SEM, 89.8 +/- 11.4) groups compared with controls (mean +/- SEM, 32.1 +/- 1.8) (P < .05). CD18 expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 134.2 +/- 14.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 200.2 +/- 17.2) compared with controls (mean +/- SEM, 217.6 +/- 16.5) (P < .05). CD11b expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 25.8 +/- 2.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 36.4 +/- 0.9) compared with controls (mean +/- SEM, 39.7 +/- 3.9) (P < .05).
Radiodetoxified endotoxin reduces mortality rates from bacterial peritonitis when given at least 72 hours prior to a bacterial inoculum. Tolerance to subsequent LPS challenge is associated with an abrogation of the reduced peripheral monocyte CD11b and CD18 expression observed in native LPS-stimulated mice but is not associated with changes in polymorphonuclear leukocyte CD11b and CD18 expression. The mechanism of the observed RDE-induced monocyte hyporesponsiveness to LPS and its possible protective effect is uncertain and requires further investigation.
验证以下假说，即经辐射解毒的内毒素（RDE）预处理可能部分通过改变白细胞黏附受体表达来减轻后续感染的有害影响，并研究RDE诱导内毒素耐受的细胞机制。
为评估RDE预处理对细菌性腹膜炎死亡率的影响，请在注射RDE后的0、1、3和5天，每隔一段时间给大鼠腹腔内接种钡剂粪便接种物。然后进行实验以测试对白细胞黏附受体表达的影响。两组小鼠接受生理盐水，一组接受RDE。72小时后，一组接受生理盐水（生理盐水/生理盐水组），其他组接受脂多糖（LPS）（生理盐水/LPS组和RDE/LPS组）。注射后1小时获取外周血白细胞，通过流式细胞术分析CD11b和CD18表达。
实验室动物研究。
在接种前0小时和24小时用RDE预处理的大鼠中，存活率没有提高（分别为0%和7%）。在接种前72小时和120小时用RDE预处理的大鼠中，存活率分别为47%（P <.01）和60%（P <.01）。与对照组（平均值±标准误，176.4±18.9）相比，RDE/LPS组（平均值±标准误，300.3±32.9）和生理盐水/LPS组（平均值±标准误，360.4±59.9）中多形核白细胞上的CD18表达增加了两倍（P <.05）。与对照组（平均值±标准误，32.1±1.8）相比，RDE/LPS组（平均值±标准误，91.3±8.1）和生理盐水/LPS组（平均值±标准误，89.8±11.4）中多形核白细胞上的CD11b表达增加了三倍（P <.05）。与对照组（平均值±标准误，217.6±16.5）相比，生理盐水/LPS组中单核细胞上的CD18表达降低（平均值±标准误，134.2±14.2），而RDE/LPS组中单核细胞上的CD18表达没有变化（平均值±标准误，200.2±17.2）（P <.05）。与对照组（平均值±标准误，39.7±3.9）相比，生理盐水/LPS组中单核细胞上的CD11b表达降低（平均值±标准误，25.8±2.2），而RDE/LPS组中单核细胞上的CD11b表达没有变化（平均值±标准误，36.4±0.9）（P <.05）。
在细菌接种前至少72小时给予经辐射解毒的内毒素可降低细菌性腹膜炎的死亡率。对随后LPS刺激的耐受性与天然LPS刺激的小鼠中观察到的外周单核细胞CD11b和CD18表达降低的消除有关，但与多形核白细胞CD11b和CD18表达的变化无关。观察到的RDE诱导的单核细胞对LPS反应性降低的机制及其可能的保护作用尚不确定，需要进一步研究。
