Sanford Research/USD, Department of Pediatrics, Sanford School of Medicine of The University of South Dakota, Sioux Falls, SD 57104, USA.
Drug Discov Today. 2010 Jul;15(13-14):531-9. doi: 10.1016/j.drudis.2010.05.013.
Pathogenesis of type 1 diabetes involves the activation of autoimmune T cells, consequent homing of activated lymphocytes to the pancreatic islets and ensuing destruction of insulin-producing b cells. Interaction between activated lymphocytes and endothelial cells in the islets is the hallmark of the homing process. Initial adhesion, firm adhesion and diapedesis of lymphocytes are the three crucial steps involved in the homing process. Cell-surface receptors including integrins, selectins and hyaluronate receptor CD44 mediate the initial steps of homing. Diapedesis relies on a series of proteolytic events mediated by matrix metalloproteinases. Here, molecular mechanisms governing transendothelial migration of the diabetogenic effector cells are discussed and resulting pharmacological strategies are considered.
1 型糖尿病的发病机制涉及自身免疫性 T 细胞的激活，随后激活的淋巴细胞归巢到胰岛，导致胰岛素分泌细胞的破坏。激活的淋巴细胞与胰岛内皮细胞的相互作用是归巢过程的标志。初始黏附、牢固黏附和淋巴细胞的穿越是归巢过程中三个关键步骤。包括整合素、选择素和透明质酸受体 CD44 在内的细胞表面受体介导归巢的初始步骤。穿越依赖于基质金属蛋白酶介导的一系列蛋白水解事件。本文讨论了控制糖尿病效应细胞穿越血管内皮的分子机制，并考虑了由此产生的药理策略。
