Kitazawa Toshiyuki, Nakatani Yoshihiro, Fujimoto Masao, Tamura Nobuhiro, Uemura Masahito, Fukui Hiroshi
Third Department of Internal Medicine, Nara Medical University, Kashihara-shi, Nara, Japan.
Alcohol Clin Exp Res. 2003 Aug;27(8 Suppl):72S-75S. doi: 10.1097/01.ALC.0000078611.55696.F0.
It is suggested that endotoxin, proinflammatory cytokines, and lipopolysaccharide-binding protein (LBP) play an important role in the development of alcoholic liver disease. Our previous study showed that splenic macrophages were important for endotoxin uptake and excessive production of tumor necrosis factor (TNF) in rats given large amounts of alcohol. To study the pathophysiological roles of macrophages in alcoholic liver diseases, we examined the production of TNF-alpha by rat Kupffer cells, splenic macrophages, and alveolar macrophages with acute alcohol loading in the presence or absence of LBP.
Kupffer cells, splenic macrophages, and alveolar macrophages were isolated from male Wistar rats given 5 mg/g body weight of ethanol intraperitoneally after an hour. The production of TNF-alpha by these cells incubated with endotoxin 100 ng/ml in the presence or absence of LBP (1% rat serum) was determined.
Acute alcohol loading did not affect the production of TNF-alpha by Kupffer cells. With acute alcohol loading, splenic macrophages tended to produce more TNF-alpha. Alveolar macrophages produced more TNF-alpha than Kupffer cells, and although the production of TNF-alpha by alveolar macrophages tended to be suppressed by acute alcohol loading, the production of TNF-alpha by alveolar macrophages still remained high in the presence of rat serum.
Splenic macrophages and alveolar macrophages may be related to excessive production of TNF-alpha in acute alcoholics with endotoxemia.
有研究表明内毒素、促炎细胞因子和脂多糖结合蛋白（LBP）在酒精性肝病的发生发展中起重要作用。我们之前的研究表明，在给予大量酒精的大鼠中，脾巨噬细胞对于内毒素摄取和肿瘤坏死因子（TNF）的过量产生至关重要。为了研究巨噬细胞在酒精性肝病中的病理生理作用，我们检测了在有或无LBP存在的情况下，急性酒精负荷时大鼠枯否细胞、脾巨噬细胞和肺泡巨噬细胞中TNF-α的产生情况。
从雄性Wistar大鼠中分离出枯否细胞、脾巨噬细胞和肺泡巨噬细胞，这些大鼠在一小时后腹腔注射5mg/g体重的乙醇。测定在有或无LBP（1%大鼠血清）存在的情况下，这些细胞与100ng/ml内毒素孵育时TNF-α的产生情况。
急性酒精负荷不影响枯否细胞产生TNF-α。急性酒精负荷时，脾巨噬细胞倾向于产生更多的TNF-α。肺泡巨噬细胞产生的TNF-α比枯否细胞多，并且尽管急性酒精负荷倾向于抑制肺泡巨噬细胞产生TNF-α，但在有大鼠血清存在的情况下，肺泡巨噬细胞产生的TNF-α仍然很高。
脾巨噬细胞和肺泡巨噬细胞可能与伴有内毒素血症的急性酒精中毒患者体内TNF-α的过量产生有关。
