Involvement of beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the development of diabetes in obese diabetic mice.
Involvement of beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the development of diabetes in obese diabetic mice.
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DOI：
10.2337/diabetes.46.10.1542
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发表时间：
1997
期刊：
影响因子：
7.7
通讯作者：
X. D. Yang;H. Sytwu;H. Mcdevitt;S. Michie
中科院分区：
文献类型：
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作者：
X. D. Yang;H. Sytwu;H. Mcdevitt;S. Michie
非肥胖糖尿病（NOD）小鼠发展自身免疫介导的胰岛淋巴细胞炎症（胰岛素炎），导致β细胞破坏和糖尿病的发展。炎症胰岛显示淋巴细胞α 4 β 7整合素和内皮粘膜寻址蛋白细胞粘附分子-1 （MAdCAM-1）的表达，这些粘附分子参与淋巴细胞向粘膜淋巴组织的组织选择性迁移。为了阐明粘膜淋巴细胞/内皮粘附系统在糖尿病发展中的作用，我们用抗β 7整合素或MAdCAM-1的单克隆抗体治疗NOD小鼠。在7 - 28天或8 - 12周的小鼠中，使用任一抗体均可显著且长期地预防糖尿病和胰岛素的自发发展。相反，两种治疗方法都不能预防唾液腺炎症（涎腺炎）的发展，表明这种作用是组织选择性的。单克隆抗体治疗对外周血淋巴细胞的数量或表型或对胰岛或外源抗原的免疫反应没有明显的影响。这些数据表明，参与淋巴细胞向粘膜淋巴组织迁移的淋巴细胞和内皮粘附分子在NOD小鼠糖尿病的发生中发挥了作用。此外，研究结果表明，用针对组织选择性淋巴细胞或内皮粘附分子的抗体治疗人类可能会选择性地抑制自身免疫性疾病（如糖尿病）的发展。
Nonobese diabetic (NOD) mice develop autoimmune-mediated lymphocytic inflammation of pancreatic islets (insulitis) that leads to beta-cell destruction and development of diabetes. Inflamed islets show expression of lymphocyte alpha 4 beta 7 integrin and endothelial mucosal addressin cell adhesion molecule-1 (MAdCAM-1), adhesion molecules involved in tissue-selective migration of lymphocytes to mucosal lymphoid tissues. To elucidate the roles of the mucosal lymphocyte/endothelial adhesion system in the development of diabetes, we treated NOD mice with monoclonal antibody against beta 7 integrin or MAdCAM-1. Treatment of mice from age 7 to 28 days or 8 to 12 weeks with either antibody led to significant and long-standing protection against the spontaneous development of diabetes and insulitis. In contrast, neither treatment prevented the development of salivary gland inflammation (sialadenitis), indicating that the effect was tissue-selective. Monoclonal antibody treatment had no demonstrable effect on numbers or phenotypes of peripheral lymphocytes or on the immune response to pancreatic islet or exogenous antigens. These data indicate that lymphocyte and endothelial adhesion molecules involved in the migration of lymphocytes into mucosal lymphoid tissues play a role in the development of diabetes in NOD mice. Moreover, the results suggest that treatment of humans with antibodies against tissue-selective lymphocyte or endothelial adhesion molecules may selectively inhibit the development of autoimmune diseases such as diabetes.