Blockade of PSGL-1 attenuates CD14+monocytic cell recruitment in intestinal mucosa and ameliorates ileitis in SAMP1/Yit mice
Blockade of PSGL-1 attenuates CD14+monocytic cell recruitment in intestinal mucosa and ameliorates ileitis in SAMP1/Yit mice
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DOI：
10.1189/jlb.0204104
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发表时间：
2005-03-01
影响因子：
5.5
通讯作者：
Miura, S
中科院分区：
文献类型：
--
作者：
Inoue, T;Tsuzuki, Y;Miura, S
克罗恩病（CD）的发病机制尚不清楚。然而，单核细胞和巨噬细胞被认为在粘膜炎症的发展中发挥重要作用。因此，在这项研究中，我们研究了单核细胞-内皮细胞相互作用在衰老加速小鼠 P1 (SAMP1)/Yit 小鼠（自发性回肠炎的小鼠模型）中的作用。将从 AKR/J（对照）小鼠的脾脏和肠系膜淋巴结中分离出的荧光标记的 CD14+ 单核细胞注射到受体（AKR/J 和 SAMP1/Yit）小鼠的尾静脉中，并使用活体显微镜监测派尔氏斑毛细血管后微静脉（PCV）、粘膜下微静脉和回肠末端绒毛微血管的迁移。 SAMP1/Yit 小鼠中派尔氏淋巴结 PCV 和回肠末端微血管中 CD14+ 单核细胞的滚动和粘附增加。免疫组织化学研究显示，SAMP1/Yit 小鼠回肠末端 P-选择素糖蛋白-1 (PSGL-1)、P-选择素和血管细胞粘附分子-1 的表达增加。针对这三种粘附分子的抗体显着抑制 CD14+ 单核细胞与派尔氏集结的 PCV 和回肠末端微血管的粘附，用抗 PSGL-1 单克隆抗体 (mAb) 处理显示出最强的抑制效果。抗 PSGL-1 mAb 还可减弱肠粘膜微血管中的 T 细胞粘附。此外，定期施用抗PSGL-1 mAb 7周可显着改善SAMP1/Yit小鼠的回肠炎。结果表明，PSGL-1-P-选择素相互作用在CD小鼠模型中的单核细胞-内皮细胞相互作用和回肠炎的发展中发挥重要作用，并且阻断这种粘附分子可能是治疗CD的新策略。
The pathogenesis of Crohn's disease (CD) is not known. However, monocytes and macrophages are thought to play important roles in the development of mucosal inflammation. Therefore, in this study, we examined the role of monocyte-endothelial cell interactions in senescence-accelerated mouse P1 (SAMP1)/Yit mice, a murine model of spontaneous ileitis. Fluorescence-labeled CD14+ monocytic cells isolated from the spleen and mesenteric lymph nodes of AKR/J (control) mice were injected into the tail veins of recipient (AKR/J and SAMP1/Yit) mice, and migration in the postcapillary venules (PCV) of Peyer's patches, submucosal venules, and villus microvessels of the terminal ileum was monitored by using an intravital microscope. Rolling and adhesion of CD14+ monocytic cells in the PCV of Peyer's patches and microvessels of the terminal ileum were increased in SAMP1/Yit mice. An immunohistochemical study showed increased expression of P-selectin glycoprotein-1 (PSGL-1), P-selectin, and vascular cell adhesion molecule-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against these three adhesion molecules significantly inhibited adhesion of CD14+ monocytic cells to the PCV of Peyer's patches and microvessels of the terminal ileum, treatment with an anti-PSGL-1 monoclonal antibody (mAb) showing the strongest suppressive effect. Anti-PSGL-1 mAb also attenuated T cell adhesion in microvessels of intestinal mucosa. In addition, periodical administration of an antiPSGL-1 mAb for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice. The results suggest that PSGL-1-P-selectin interaction plays an important role in monocyte-endothelial cell interactions and the development of ileitis in a murine model of CD and that the blockade of this adhesion molecule may be a novel strategy for treating CD.