Palmen M J, Dijkstra C D, van der Ende M B, Peña A S, van Rees E P
Department of Cell Biology/Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Clin Exp Immunol. 1995 Aug;101(2):351-6. doi: 10.1111/j.1365-2249.1995.tb08363.x.
The influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel disease (IBD). A membrane protein involved in the monocyte/neutrophil adherence to endothelium is CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present study the role of CD11b/CD18 in experimental IBD was studied by treatment with ED7 and OX42, two MoAbs against CD11b/CD18. Colitis was induced in rats by a single, rectal administration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol 30%. Two hours before and 3 days after induction of colitis, the animals were given an i.v. dose of 0.5 mg of either ED7 or OX42 in 1 ml PBS. Controls received PBS or an irrelevant MoAb. Four days after the last treatment with the antibodies, the rats were killed, and macroscopic damage scores of the colon were determined. Macrophages and granulocytes were studied by immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS), and myeloperoxidase (MPO) activity in colonic tissue was measured. After treatment with ED7 and OX42 the mean damage score of the colon was reduced from 4.2 in IBD animals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and a decrease in the number of ulcerations were observed compared with PBS-treated rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the submucosa was enormously reduced, as well as MPO activity in the colonic tissue. These results show that treatment with MoAbs against CD11b/CD18 reduces clinical signs of experimental IBD in rats by a partial blockade of infiltrating macrophages and granulocytes.
单核细胞和中性粒细胞流入炎症组织可能是炎症性肠病（IBD）发病机制中的一个重要方面。参与单核细胞/中性粒细胞与内皮细胞黏附的一种膜蛋白是CD11b/CD18或αMβ2（补体受体3型 = CR3）。在本研究中，通过用ED7和OX42（两种抗CD11b/CD18的单克隆抗体）处理来研究CD11b/CD18在实验性IBD中的作用。通过单次直肠给予溶解于30%乙醇中的30 mg 2,4,6-三硝基苯磺酸（TNBS）在大鼠中诱导结肠炎。在诱导结肠炎前2小时和诱导后3天，给动物静脉注射1 ml PBS中含有的0.5 mg ED7或OX42。对照组接受PBS或无关单克隆抗体。在用抗体进行最后一次治疗后4天，处死大鼠，测定结肠的宏观损伤评分。通过免疫组织化学研究巨噬细胞和粒细胞，并通过交互式图像分析系统（IBAS）进行定量，测量结肠组织中的髓过氧化物酶（MPO）活性。用ED7和OX42处理后，结肠的平均损伤评分分别从IBD动物的4.2降至1.0和1.3。与PBS处理的大鼠相比，观察到溃疡面积更小且溃疡数量减少。此外，黏膜下层浸润的单核细胞和白细胞数量以及结肠组织中的MPO活性大幅降低。这些结果表明，用抗CD11b/CD18单克隆抗体治疗可通过部分阻断浸润的巨噬细胞和粒细胞来减轻大鼠实验性IBD的临床症状。
