Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats
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DOI:
10.3748/wjg.v11.i29.4505
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发表时间:
2005-08-07
影响因子:
4.3
通讯作者:
Sekine, Ichiro
Sekine, Ichiro
中科院分区:
医学2区
文献类型:
--
作者:
Shichijo, Kazuko;Makiyama, Kazuya;Sekine, Ichiro

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目的:制备大鼠嗜酸性粒细胞阳离子蛋白(ECP)抗体,观察其对葡聚糖硫酸钠(DSS)诱导的大鼠结肠炎的治疗作用。用3%DSS饮水染毒大鼠7 d,并分别给予抗体或正常血清。结肠进行组织学检查,并与临床症状。结果:ECP抗体在损伤的结肠粘膜中可染色到损伤的隐窝周围活化的嗜酸性粒细胞。抗体治疗降低了结肠溃疡和急性临床症状(腹泻和/或血便)的严重程度。体重增加显着更大,结肠长度显着长于抗ECP治疗的大鼠比正常血清治疗的大鼠。ECP在活化的嗜酸性粒细胞中的表达与糜烂和炎症的存在相关。与正常血清处理的大鼠相比,抗ECP处理的大鼠再生表面上皮中Ki-67阳性细胞的数量增加。Western blot分析显示,巨噬细胞移动抑制因子(MIF)的表达减少,在抗ECP治疗rats.CONCLUSION:我们的研究结果表明,治疗与ECP抗体,改善DSS诱导的大鼠结肠炎,可能是通过增加结肠上皮细胞的再生活性和下调免疫反应,并表明,抗ECP可能促进溃疡性结肠炎(UC)患者肠伤口愈合。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
AIM: To produce an antibody against rat eosinophil cationic protein (ECP) and to examine the effects of the antibody in rats with dextran sulfate sodium (DSS)-induced colitis.METHODS: An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were examined histologically and correlated with clinical symptoms. Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation.RESULTS: The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa. Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms (diarrhea and/or bloodstained stool). Body weight gain was significantly greater and the colon length was significantly longer in anti-ECP-treated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor (MIF) in anti-ECP-treated rats.CONCLUSION: Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response, and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis (UC). (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.