Monoclonal antibodies specific for beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) reduce inflammation in the colon of scid mice reconstituted with CD45RBhigh CD4+ T cells.
Monoclonal antibodies specific for beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) reduce inflammation in the colon of scid mice reconstituted with CD45RBhigh CD4+ T cells.
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DOI：
10.4049/jimmunol.158.5.2099
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发表时间：
1997-03
影响因子：
4.4
通讯作者：
D. Picarella;P. Hurlbut;J. Rottman;Xiaojie Shi;E. Butcher;D. Ringler
中科院分区：
文献类型：
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作者：
D. Picarella;P. Hurlbut;J. Rottman;Xiaojie Shi;E. Butcher;D. Ringler
粘蛋白地址素细胞粘附分子-1（MAdCAM-1）是在粘膜组织中的内皮上表达的粘附蛋白，其已被证明在淋巴细胞选择性归巢至肠粘膜和相关淋巴组织中起重要作用。为了确定MAdCAM-1或其配体α 4 β 7是否是肠道相关炎症治疗干预的合适靶点，我们测试了β 7整联蛋白和MAdCAM-1特异性大鼠mAb抑制scid小鼠慢性结肠炎症的能力，scid小鼠用富含CD 45 RB高亚群的CD 4 + T细胞重建。β 7和MAdCAM-1特异性抗体阻断了淋巴细胞向结肠炎结肠的募集，更重要的是，这些抗体显著降低了该动物模型中结肠炎性疾病的严重程度。因此，由α 4 β 7和MAdCAM介导的粘附相互作用密切参与慢性炎性疾病中白细胞向肠道的募集，并且可能是炎性肠病患者的相关治疗靶点。
Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is an adhesion protein expressed on endothelium in mucosal tissues that has been shown to play an important role in the selective homing of lymphocytes to intestinal mucosa and associated lymphoid tissue. To determine whether MAdCAM-1 or its ligand alpha 4 beta 7 would be appropriate targets for therapeutic intervention in gut-associated inflammation, we tested the ability of rat mAbs specific for beta 7 integrin and MAdCAM-1 to inhibit chronic colonic inflammation in scid mice reconstituted with CD4+ T cells enriched for the CD45RBhigh subpopulation. Abs specific for beta 7 and MAdCAM-1 blocked recruitment of lymphocytes to the colitic colon, and more importantly, these Abs significantly reduced the severity of colonic inflammatory disease in this animal model. Therefore, the adhesive interactions mediated by alpha 4 beta 7 and MAdCAM are intimately involved in leukocyte recruitment to gut in chronic inflammatory disease and may be relevant therapeutic targets for patients with inflammatory bowel disease.