Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis
Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis
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DOI：
10.1046/j.1440-1746.2003.03088.x
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发表时间：
2003-09-01
影响因子：
4.1
通讯作者：
Miura, S
中科院分区：
文献类型：
--
作者：
Matsuzaki, K;Hokari, R;Miura, S
背景与目的：溃疡性结肠炎(UC)的发病机制尚不清楚，但T淋巴细胞在结肠粘膜的异常浸润与黏膜组织损伤有关。T辅助细胞(H)1/Th2失衡所致的细胞因子产生异常可能在结肠黏膜持续炎症中起重要作用。本研究通过检测Th1细胞趋化因子受体5(CCR5)和Th2细胞趋化因子受体同源分子(CRTH2)的表达，分析UC患者结肠黏膜Th1/Th2应答受损情况。用链霉亲和素生物素标记法对高碘酸盐、赖氨酸-多聚甲醛固定的连续冰冻切片进行免疫组织化学分析。以抗CD4、CCR5或CRTH2的单抗为一抗。结果：UC患者炎症黏膜中CD4、CCR5、CRTH2阳性细胞数明显增多，且与疾病活动程度呈正相关。结论：UC患者的结肠黏膜可能存在明显的Th1反应，而Th2反应主要发生在炎症程度较轻的结肠黏膜。结肠粘膜Th1/Th2失衡可能与UC的病情进展有关。(C)2003年Blackwell出版亚洲私人有限公司。
Background and Aim: The pathogenesis of ulcerative colitis (UC) is unclear, but abnormal infiltration of T lymphocytes in the colonic mucosa has been implicated in the mucosal tissue damage. The abnormal cytokine production because of a T helper (h)1/Th2 imbalance may play an important role in continuing inflammation in the colonic mucosa. In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients.Methods: Tissue samples were obtained by colonic biopsies from patients with UC or colonic polyps, with informed consent. Immunohistochemical analysis was performed on periodate, lysine-paraformaldehyde-fixed serial cryostat sections using the labeled streptavidin biotin method. Monoclonal antibodies against CD4, CCR5 or CRTH2 were used as primary antibodies. The number of cells expressing CD4, CCR5 or CRTH2 per unit area was calculated by using an image analyzer.Results: In the patients with UC, the numbers of CD4- and CCR5-positive cells were significantly increased in inflamed mucosa, and appeared to be correlated with the disease activity. The infiltration of CRTH2-positive cells was predominantly observed in the mildly inflamed or the margin of inflamed mucosa of UC patients.Conclusion: There is a possibility that Th1 responses significantly occur in colonic mucosa with severe inflammation, while Th2 responses mainly occur with mild inflammation in UC patients. The Th1/Th2 imbalance in colonic mucosa may be related to the disease progression of UC. (C) 2003 Blackwell Publishing Asia Pty Ltd.