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Mucosal Vaccination Increases Endothelial Expression of Mucosal Addressin Cell Adhesion Molecule 1 in the Human Gastrointestinal Tract

机译:粘膜疫苗接种增加人类胃肠道粘膜Addressin细胞粘附分子1的内皮表达。

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摘要

Homing of leukocytes to various tissues is dependent on the interaction between homing receptors on leukocytes and their ligands, addressins, on endothelial cells. Mucosal immunization results in homing of antigen-specific lymphocytes back to the mucosa where they first encountered the antigen. However, it is unknown whether this homing of antigen-specific cells is mediated by an altered endothelial addressin expression after vaccination. Using different immunization routes with an oral cholera vaccine, we show that the endothelial expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is increased in the gastric and upper small intestinal mucosae after immunization through various local routes in the upper gastrointestinal tract. In contrast, rectal immunization did not influence the levels of MAdCAM-1 in the gastric or duodenal mucosa. Furthermore, we show that MAdCAM-1 can be induced on human endothelial cells by tumor necrosis factor alpha (TNF-α) and gamma interferon. The vaccine component cholera toxin B subunit (CTB) increased MAdCAM-1 expression on endothelial cells in cultured human gastric explants, an effect that seemed to be mediated by TNF-α. In conclusion, MAdCAM-1 expression is increased in the upper gastrointestinal tract after local immunizations with a vaccine containing CTB. This strongly suggests the involvement of MAdCAM-1 in the preferential homing of mucosal lymphocytes to their original site of activation.
机译:白细胞向各种组织的归巢取决于白细胞上的归巢受体与其内皮细胞上的配体地址蛋白之间的相互作用。粘膜免疫导致抗原特异性淋巴细胞归巢回到它们首次遇到抗原的粘膜。然而,尚不知道抗原特异性细胞的这种归巢是否通过疫苗接种后内皮地址蛋白表达的改变来介导。通过口服霍乱疫苗使用不同的免疫途径,我们显示了通过上胃肠道的各种局部途径免疫后,胃和上小肠粘膜的粘膜寻址蛋白细胞粘附分子1(MAdCAM-1)的内皮表达增加。相反,直肠免疫不影响胃或十二指肠粘膜中MAdCAM-1的水平。此外,我们表明,肿瘤坏死因子α(TNF-α)和γ干扰素可以在人内皮细胞上诱导MAdCAM-1。疫苗成分霍乱毒素B亚基(CTB)增加了培养的人胃外植体中内皮细胞MAdCAM-1的表达,这种作用似乎是由TNF-α介导的。总之,用含CTB的疫苗进行局部免疫后,MAdCAM-1的表达在上消化道增加。这强烈表明MAdCAM-1参与了粘膜淋巴细胞向其原始激活位点的优先归巢。

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