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抗CD11b(αM-MAC-1)和抗CD54(ICAM-1)单克隆抗体对吲哚美辛诱导的大鼠慢性回肠炎的影响。

Effect of anti-CD11b (alphaM-MAC-1) and anti-CD54 (ICAM-1) monoclonal antibodies on indomethacin induced chronic ileitis in rats.

作者信息

Krieglstein C F, Anthoni C, Laukötter M G, Rijcken E, Spiegel H U, Senninger N, Schürmann G

机构信息

Department of General Surgery, Westfalian Wilhelm's University, Münster, Germany.

出版信息

Int J Colorectal Dis. 1999 Nov;14(4-5):219-23. doi: 10.1007/s003840050214.

DOI:10.1007/s003840050214
PMID:10647630
Abstract

Leukocyte emigration from blood to sites of inflammation involves sequential interaction of specific adhesion molecules expressed by both leukocytes and endothelial cells. The central steps in leukocyte-endothelial adhesive interactions are leukocyte rolling, sticking, and transmigration. This study investigated the effect of monoclonal antibodies against CD54 (ICAM-1) and CD11b (alphaM-chain of MAC-1) on intestinal inflammation. Anti-CD54 and anti-CD11b were tested in rats with indomethacin-induced chronic ileitis. Macroscopic changes were assessed by a modified version of the Wallace et al. score. Leukocyte rolling and sticking were investigated by intravital microscopy. Results show that indomethacin administration led to a chronic inflammatory response characterized by significant increase (P<0.05) in rolling (from 5.41+/-2.87 to 32.41+/-15.03 100 microm(-1) s(-1)) and sticking (from 0.16+/-0.18 to 9.11+/-5.3 100 microm(-1) s(-1)) leukocytes. After antibody treatment only the anti-CD11b group showed significant (P<0.05) reduction in rolling (from 32.41+/-15.03 to 6.6+/-2.7 100 microm(-1) s-1) and sticking (from 9.11+/-5.3 to 0.07+/-0.09 100 microm(-1) s-1) leukocytes. This was also the case for macroscopic changes. Indomethacin led to a rise in the Wallace score from 0 to 4.29+/-0.76 points (P<0.05) and anti-CD11b to a reduction from 4.29+/-0.76 to 1.29+/-1.11 points (P<0.05). Anti-CD54 and combined anti-CD11b/CD54 administration was not followed by significant changes. Therefore we suggest that leukocyte-based CD11b but not endothelial-based CD54 contributes most to leukocyte adhesion in the setting of indomethacin-induced ileitis in rats.

摘要

白细胞从血液迁移至炎症部位涉及白细胞和内皮细胞所表达的特定黏附分子之间的一系列相互作用。白细胞与内皮细胞黏附相互作用的核心步骤包括白细胞滚动、黏附及迁移。本研究调查了抗CD54(细胞间黏附分子-1)和抗CD11b(巨噬细胞-1抗原的αM链)单克隆抗体对肠道炎症的影响。在吲哚美辛诱导的慢性回肠炎大鼠中测试了抗CD54和抗CD11b。通过对Wallace等人的评分进行修改来评估宏观变化。通过活体显微镜观察白细胞滚动和黏附情况。结果显示,给予吲哚美辛导致慢性炎症反应,其特征为滚动(从5.41±2.87增至32.41±15.03 100μm⁻¹ s⁻¹)和黏附(从0.16±0.18增至9.11±5.3 100μm⁻¹ s⁻¹)的白细胞显著增加(P<0.05)。抗体治疗后,仅抗CD11b组的滚动(从32.41±15.03降至6.6±2.7 100μm⁻¹ s⁻¹)和黏附(从9.11±5.3降至0.07±0.09 100μm⁻¹ s⁻¹)白细胞显著减少(P<0.05)。宏观变化情况也是如此。吲哚美辛使Wallace评分从0升至4.29±0.76分(P<0.05),而抗CD11b使其从4.29±0.76降至1.29±1.11分(P<0.05)。给予抗CD54以及联合给予抗CD11b/CD54后未出现显著变化。因此,我们认为在吲哚美辛诱导的大鼠回肠炎中,基于白细胞的CD11b而非基于内皮细胞的CD54对白细胞黏附起主要作用。

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