Mononuclear leukocytes bind to specific hyaluronan structures on colon mucosal smooth muscle cells treated with polyinosinic acid:: Polycytidylic acid -: Inter-α-trypsin inhibitor is crucial to structure and function
Mononuclear leukocytes bind to specific hyaluronan structures on colon mucosal smooth muscle cells treated with polyinosinic acid:: Polycytidylic acid -: Inter-α-trypsin inhibitor is crucial to structure and function
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DOI：
10.1016/s0002-9440(10)63636-x
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发表时间：
2003-07-01
影响因子：
6
通讯作者：
Strong, SA
中科院分区：
文献类型：
--
作者：
de la Motte, CA;Hascall, VC;Strong, SA
炎症性肠病(IBD)是一种慢性疾病，其病因与引发事件有关，包括病毒感染，这些事件会导致遗传易感者的免疫调节功能障碍。特征性的病理改变包括单核细胞进入肠粘膜的增多以及粘膜平滑肌细胞(M-SMC)的增生。病毒感染或病毒模拟[PolyI：C]处理体外培养的人结肠M-SMCs可增加细胞表面透明质酸(HA)，未激活的单核白细胞通过涉及HA结合受体CD44的相互作用与病毒诱导的RA结构结合。在这项研究中，共聚焦显微镜显示，经Poly I：C处理的M-SMC表面在3小时内HA增加，排列成衣状结构。17小时后，新的、长的缆索结构明显，这些缆索主要负责调节白细胞的粘连。免疫组织化学染色显示包被样结构和缆索结构中均含有IalphaI复合体。M-SMC与PolyI：C和多克隆共处理。抗IalphaI抗体在外套中显示RA，但线缆减少，它们与白细胞的结合明显少于M-SMC；单独使用PolyI：C处理。Western印迹数据表明IalphaI的重链与电缆结构特别相关。对IBD患者组织切片的染色表明，炎症的结肠组织中存在RA，并显示与同一患者的非炎症切片相比，炎症的IBD标本的粘膜中HA相关的IalphaI染色增加，这在体外观察和IBD炎症过程的进展之间建立了可能的联系。
Inflammatory bowel disease (IBD) is a chronic disorder whose etiology is linked to triggering events, including viral infections, that lead to immunoregulatory dysfunction in genetically susceptible people. Characteristic pathological changes include increased mononuclear leukocyte influx into the intestinal mucosa as well as mucosal smooth muscle cell (M-SMC) hyperplasia. Virus infection or viral mimic [polyinosinic acid:polycytidylic acid (polyI:C)] treatment of human colon M-SMCs in vitro increases cell surface hyaluronan (HA), and nonactivated mononuclear leukocytes bind to virus-induced RA structures by interactions that involve the HA-binding receptor CD44. In this study, confocal microscopy reveals increased HA on poly I:C-treated M-SMC surfaces within 3 hours, arrayed in coat-like structures. By 17 hours, novel, lengthy cable structures are evident, and these are primarily responsible for mediating leukocyte adhesion. Immunohistochemical staining demonstrates components of the inter-alpha-trypsin inhibitor (IalphaI) complex in both coat-like and cable structures. M-SMCs co-treated with polyI:C and a polyclonal. antibody to IalphaI display RA in coats but with diminished cables, and they bind significantly fewer leukocytes than M-SMCs; treated with polyI:C alone. Western blot data suggest that heavy chains of IalphaI are specifically associated with cable structures. Staining of tissue sections from patients with IBD demonstrates the presence of RA in inflamed colon tissue, and shows that HA-associated IalphaI staining increases in the mucosa of inflamed IBD specimens compared to noninflamed sections from the same patient, establishing a probable link between the observations in vitro and the progression of the inflammatory process in IBD.