Sadahiro M, Allen M D
Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Japan.
Nihon Kyobu Geka Gakkai Zasshi. 1994 Aug;42(8):1148-53.
Leukocyte binding to endothelial adhesion molecules has been said to be an initiating step in cardiac allograft rejection. Whether antibody blockage of leukocyte ligands, CD18, for intercellular adhesion molecule (ICAM-1) would prevent allograft rejection was studied in a rabbit heterotopic transplant model. Cervical cardiac transplant was performed between donor Staffland and New Zealand White recipient rabbits. Ten animals were treated with intravenous anti-CD8 monoclonal antibody, 60.3, at the dose of 1 mg/kg for 7 days. No immunosuppressive drugs were used. Eleven transplant controls were untreated. At 7 days, animals were sacrificed and donor heart histology was compared. Peripheral WBC counts were significantly higher in treatment group compared to untreated group on both postoperative day 2 and 7. The cellular rejection score was 30% lower in treated group than untreated (p < 0.05), demonstrating localization of lymphocytes to perivenular collections. The proportion of arteries with evidence of vasculitis was 45% lower in treated group. Results suggests that monoclonal antibody against LFA-1 (CD18) may hold promise as a therapeutic agent for both cellular and vascular rejection.
白细胞与内皮黏附分子的结合被认为是心脏同种异体移植排斥反应的起始步骤。在兔异位移植模型中，研究了针对白细胞配体CD18（细胞间黏附分子-1，ICAM-1）的抗体阻断是否能预防同种异体移植排斥反应。在供体史塔夫兰兔和新西兰白兔受体之间进行颈部心脏移植。10只动物静脉注射剂量为1mg/kg的抗CD8单克隆抗体60.3，持续7天。未使用免疫抑制药物。11只移植对照组未接受治疗。在第7天，处死动物并比较供体心脏组织学。术后第2天和第7天，治疗组的外周白细胞计数显著高于未治疗组。治疗组的细胞排斥评分比未治疗组低30%（p<0.05），表明淋巴细胞定位于静脉周围聚集处。治疗组有血管炎证据的动脉比例低45%。结果表明，抗淋巴细胞功能相关抗原-1（LFA-1，CD18）单克隆抗体有望成为治疗细胞和血管排斥反应的药物。
