Noguchi Atsushi, Watanabe Kenji, Narumi Shosaku, Yamagami Hirokazu, Fujiwara Yasuhiro, Higuchi Kazuhide, Oshitani Nobuhide, Arakawa Tetsuo
Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
J Gastroenterol. 2007 Dec;42(12):947-56. doi: 10.1007/s00535-007-2118-9. Epub 2007 Dec 25.
To clarify which types of cells produce interferon-gamma-inducible protein 10 (IP-10) and whether IP-10 is associated with the development of ulcerative colitis (UC), we investigated IP-10 production in UC patients.
Serum IP-10 levels were measured using enzyme-linked immunosorbent assay in 29 patients with active and 21 with inactive UC and in 20 controls. The production of IP-10 by granulocytes and monocytes adsorbed to G-1 beads was examined. In 21 active UC patients treated with granulocyte and monocyte/macrophage adsorptive apheresis (GMA), serum IP-10 levels were measured before and after treatment. IP-10-positive cells in UC mucosa were also examined immunohistochemically using tissues obtained by surgical resection and colonoscopic biopsies.
Serum IP-10 levels in active UC patients were significantly higher than those in inactive patients, although even in the latter the levels were increased compared with those in controls. IP-10 production by granulocytes and monocytes in active UC patients was significantly higher than that in controls. Furthermore, the number of IP-10-positive cells was elevated in the colonic mucosa of patients with active UC, and one of the main subpopulations of IP-10-positive cells was granulocytes. Serum IP-10 levels decreased following GMA treatment in responders, but not in nonresponders. Interestingly, serum IP-10 levels before GMA were higher in responders than in nonresponders. In parallel with the serum levels, IP-10-positive cells also decreased following GMA treatment.
Serum IP-10 levels reflected UC disease activity, and the source of IP-10 was granulocytes and monocytes. Furthermore, serum IP-10 levels may be a marker for the responsiveness of patients to GMA treatment.
为了明确哪些类型的细胞产生γ-干扰素诱导蛋白10(IP-10)以及IP-10是否与溃疡性结肠炎(UC)的发病相关,我们对UC患者的IP-10产生情况进行了研究。
采用酶联免疫吸附测定法检测29例活动期UC患者、21例非活动期UC患者及20例对照者的血清IP-10水平。检测吸附于G-1珠上的粒细胞和单核细胞产生IP-10的情况。对21例接受粒细胞和单核细胞/巨噬细胞吸附性血液成分分离术(GMA)治疗的活动期UC患者,在治疗前后检测其血清IP-10水平。还采用手术切除及结肠镜活检获取的组织,通过免疫组织化学方法检测UC黏膜中IP-10阳性细胞。
活动期UC患者的血清IP-10水平显著高于非活动期患者,不过即使是非活动期患者,其血清IP-10水平也高于对照者。活动期UC患者的粒细胞和单核细胞产生IP-10的水平显著高于对照者。此外,活动期UC患者结肠黏膜中IP-10阳性细胞数量增加,且IP-10阳性细胞的主要亚群之一是粒细胞。GMA治疗后,有反应者的血清IP-10水平下降,无反应者则未下降。有趣的是,GMA治疗前,有反应者的血清IP-10水平高于无反应者。与血清水平一致,GMA治疗后IP-10阳性细胞也减少。
血清IP-10水平反映UC疾病活动情况,IP-10的来源是粒细胞和单核细胞。此外,血清IP-10水平可能是患者对GMA治疗反应性的一个标志物。