TREATMENT WITH ANTI-CR3 ANTIBODIES ED7 AND ED8 SUPPRESSES EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN LEWIS RATS
TREATMENT WITH ANTI-CR3 ANTIBODIES ED7 AND ED8 SUPPRESSES EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN LEWIS RATS
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DOI：
10.1002/eji.1830230321
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发表时间：
1993-03-01
影响因子：
5.4
通讯作者：
DIJKSTRA, CD
中科院分区：
文献类型：
--
作者：
HUITINGA, I;DAMOISEAUX, JGMC;DIJKSTRA, CD
实验性变态反应性脑脊髓炎（EAE）是一种中枢神经系统（CNS）炎症性疾病。在EAE期间浸润CNS的白细胞中，存在大量巨噬细胞。这些巨噬细胞被认为在组织损伤和伴随的神经功能缺损的产生中起着至关重要的作用。巨噬细胞迁移穿过血脑屏障的机制尚不清楚。参与巨噬细胞粘附于内皮的膜蛋白包括CD 11b/CD 18整联蛋白，也称为3型补体受体（CR 3）。在这项研究中，我们表明，两个单克隆抗体（mAb）ED 7和ED 8是针对大鼠CR 3。此外，这些mAb使骨髓单核细胞向巯基乙酸盐诱导的腹膜炎的募集减少15- 33%。这表明ED 7和ED 8都干扰CR 3上的表位，其参与吞噬细胞向炎性病变的募集。静脉注射ED 7和ED 8可抑制EAE的临床体征。MRC OX-42也识别CR 3，但不能减少巯基乙酸盐诱导的吞噬细胞向腹膜的募集，对EAE也没有影响。这些发现表明，CR 3在巨噬细胞向EAE动物的发炎CNS募集中起作用，并证实了巨噬细胞在EAE临床体征产生中的作用。CR 3参与EAE期间的其他吞噬细胞免疫功能进行了讨论。
Experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS). Among the leukocytes which infiltrate the CNS during EAE, numerous macrophages are present. These macrophages are thought to play a crucial role in the generation of tissue damage and attendant neurological deficits. The mechanism by which the macrophages migrate across the blood-brain barrier is not yet clear. Membrane proteins involved in macrophage adherence to the endothelium include the CD11b/CD18 integrin, also known as the type 3 complement receptor (CR3). In this study we show that two monoclonal antibodies (mAb) ED7 and ED8 are directed against rat CR3. In addition, these mAb reduce recruitment of myelomonocytic cells towards thioglycollate induced peritonitis by 15-33%. This indicates that both ED7 and ED8 interfere with an epitope on CR3, which is involved in recruitment of phagocytes towards inflammatory lesions. Intravenous injection of ED7 and ED8 suppressed clinical signs of EAE. MRC OX-42, which also recognizes CR3, did not reduce thioglycollate-induced phagocyte recruitment into the peritoneum, and had no effect on EAE. These findings suggest that CR3 plays a role in the recruitment of macrophages towards the inflamed CNS of EAE animals, and confirm the role of macrophages in the generation of clinical signs of EAE. Involvement of CR3 in other phagocyte immune functions during EAE is discussed.