Yamada Tamaki, Takahashi Satoru, Masuda Kazuhiko, Ohara Hirotaka, Nakazawa Takahiro, Sano Hitoshi, Ando Tomoaki, Nakamura Soichi, Kobayashi Shinya, Kuno Atsushi, Aoki Shigeru, Nomura Tomoyuki, Joh Takashi, Itoh Makoto
Department of Comprehensive Medicine, Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
J Lab Clin Med. 2003 Oct;142(4):268-77. doi: 10.1016/S0022-2143(03)00132-X.
Intramural injection of peptidoglycan-polysaccharide polymers into the distal colon in rats induces granulomatous colitis associated with extracolonic manifestations. We sought to clarify the effects of Kupffer-cell depletion induced by the intravenous administration of gadolinium on colonic and extracolonic inflammation in this model. The effects of Kupffer-cell depletion on acute and chronic inflammation were evaluated 3 days and 3 weeks after injection of peptidoglycan-polysaccharide, respectively. We assessed the effects of gadolinium on colonic cytokine levels in vivo and the viability of elicited peritoneal macrophages and peptidoglycan-polysaccharide-induced production of nitrite, an indirect index of nitric oxide production, by these cells in vitro. A single injection of gadolinium caused a marked decrease in the number of Kupffer cells stained with antibodies within 3 days. Gadolinium treatment did not alter acute inflammation at 3 days. Repeated treatment with gadolinium dramatically attenuated grossly observed chronic inflammation, including thickening of colon wall, hepatic and splenic nodules, and swelling of foot joints; and significantly reduced the proportional areas occupied by granulomas in the colon, liver, and spleen at 3 weeks. These protective effects were reflected in significant reduction in colon and liver weights; gross scores; colonic myeloperoxidase activity, an indirect quantitative index of granulocyte infiltration; colonic interleukin-1beta levels; plasma nitrite and nitrate levels; and decreased tendency toward arthritis. Although gadolinium did not cause injury in elicited peritoneal macrophages in vitro, the compound dose-dependently attenuated peptidoglycan-polysaccharide-induced production of nitrite by these cells. Chronic Kupffer-cell depletion attenuates peptidoglycan-polysaccharide-induced granulomatous inflammation in the colon, liver, and spleen and reduces the incidence of arthritis, possibly by suppressing the production of interleukin-1beta and nitric oxide.
向大鼠远端结肠壁内注射肽聚糖 - 多糖聚合物可诱发伴有结肠外表现的肉芽肿性结肠炎。我们试图阐明静脉注射钆诱导的库普弗细胞耗竭对该模型中结肠和结肠外炎症的影响。分别在注射肽聚糖 - 多糖后3天和3周评估库普弗细胞耗竭对急性和慢性炎症的影响。我们评估了钆对体内结肠细胞因子水平的影响，以及对诱发的腹膜巨噬细胞活力和这些细胞在体外肽聚糖 - 多糖诱导的亚硝酸盐产生（一氧化氮产生的间接指标）的影响。单次注射钆在3天内导致用抗体染色的库普弗细胞数量显著减少。钆处理在3天时未改变急性炎症。用钆重复处理显著减轻了肉眼观察到的慢性炎症，包括结肠壁增厚、肝脾结节和足关节肿胀；并在3周时显著减少了结肠、肝脏和脾脏中肉芽肿所占的比例面积。这些保护作用体现在结肠和肝脏重量显著减轻；大体评分降低；结肠髓过氧化物酶活性（粒细胞浸润的间接定量指标）降低；结肠白细胞介素 - 1β水平降低；血浆亚硝酸盐和硝酸盐水平降低；以及关节炎倾向降低。虽然钆在体外未对诱发的腹膜巨噬细胞造成损伤，但该化合物剂量依赖性地减弱了这些细胞肽聚糖 - 多糖诱导的亚硝酸盐产生。慢性库普弗细胞耗竭可能通过抑制白细胞介素 - 1β和一氧化氮的产生来减轻肽聚糖 - 多糖诱导的结肠、肝脏和脾脏的肉芽肿性炎症，并降低关节炎的发生率。
