Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis.
Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis.
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DOI：
10.1084/jem.20052530
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发表时间：
2006-04-17
期刊：
影响因子：
--
通讯作者：
Ley K
中科院分区：
文献类型：
--
作者：
Rivera-Nieves J;Burcin TL;Olson TS;Morris MA;McDuffie M;Cominelli F;Ley K
L-选择素配体可能与慢性回肠炎的自发模型中炎性细胞向小肠的运输有关（即，SAMP 1/YitFc小鼠）。外周淋巴结地址素或粘膜地址素细胞粘附分子1的免疫阻断未能改善回肠炎，而P-选择素糖蛋白配体1（PSGL-1）中和衰减的过继转移和自发性疾病。免疫组化法检测肠系膜淋巴结和小肠微静脉中PSGL-1的表达，实时荧光定量逆转录聚合酶链反应（RT-PCR）和流式细胞术检测PSGL-1的表达。此外，用PSGL-1−/−骨髓重建野生型小鼠表明，PSGL-1信使RNA和PSGL-1蛋白表达仍然存在于内皮上，定位于肠系膜淋巴结和小肠内。内皮PSGL-1结合P-选择素-IgG和它的封锁或基因缺失改变了募集淋巴细胞到小肠，所揭示的活体显微镜和归巢研究。PSGL-1的内皮表达为小肠募集中涉及的各种细胞相互作用增加了新的维度。因此，PSGL-1的多重作用可以解释为什么靶向这一单一的粘附分子导致慢性小鼠回肠炎，以前抗粘附分子策略耐药的疾病的衰减。
L-selectin ligands might be relevant for inflammatory cell trafficking into the small intestine in a spontaneous model of chronic ileitis (i.e., SAMP1/YitFc mice). Immunoblockade of peripheral node addressin or mucosal addressin cell adhesion molecule 1 failed to ameliorate ileitis, whereas P-selectin glycoprotein ligand 1 (PSGL-1) neutralization attenuated both the adoptively transferred and spontaneous disease. PSGL-1 was detected in venules of mesenteric lymph node and small intestine by immunohistochemistry and confirmed by real-time reverse transcription polymerase chain reaction and flow cytometry. In addition, reconstitution of wild-type mice with PSGL-1−/− bone marrow demonstrated that PSGL-1 messenger RNA and PSGL-1 protein expression remained on endothelium, localized within mesenteric lymph node and small intestine. Endothelial PSGL-1 bound P-selectin–IgG and its blockade or genetic deletion altered the recruitment of lymphocytes to the small intestine, as revealed by intravital microscopy and homing studies. Endothelial expression of PSGL-1 adds a new dimension to the various cellular interactions involved in small intestinal recruitment. Thus, the multiple roles of PSGL-1 may explain why targeting this single adhesion molecule results in attenuation of chronic murine ileitis, a disease previously resistant to antiadhesion molecule strategies.
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