The role of Kupffer cells and regulation of neutrophil migration into the liver by macrophage inflammatory protein-2 in primary listeriosis in mice
The role of Kupffer cells and regulation of neutrophil migration into the liver by macrophage inflammatory protein-2 in primary listeriosis in mice
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DOI：
10.1046/j.1440-1827.1999.00910.x
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发表时间：
1999-06-01
影响因子：
2.2
通讯作者：
Naito, M
中科院分区：
文献类型：
--
作者：
Ebe, Y;Hasegawa, G;Naito, M
静脉注射脂质体包埋的氯膦酸盐后，小鼠枯否细胞和脾巨噬细胞的消耗严重降低了宿主对单核细胞增生李斯特菌初次感染的抵抗力。用亚致死剂量的单核细胞增生李斯特菌感染氯膦酸盐治疗的小鼠导致小鼠在3天内死亡。巨噬细胞的消耗导致肝脏和脾脏中细菌生长显着增加，但其他组织中却没有。在大量发生凋亡的肝细胞中观察到单核细胞增生李斯特菌的增殖。在单核细胞增生利斯特氏菌感染后，对照小鼠观察到中性粒细胞在肝脏中的浸润和微脓肿的快速形成。然而，库普弗细胞耗尽的小鼠肝脏中中性粒细胞的积累比对照小鼠少，单核细胞增生李斯特菌感染后，对照小鼠和库普弗细胞耗尽的小鼠肝脏中巨噬细胞炎症蛋白-2 (MIP-2) 的表达均增强。 MIP-2 也在单核细胞增生利斯特氏菌感染后在鼠肝细胞系中被诱导。中和性抗白细胞介素8受体同源抗体的施用严重消除了中性粒细胞浸润到李斯特菌感染的小鼠肝脏中，抗MIP-P抗体适度减少了肝脏中的中性粒细胞浸润和微脓肿形成。这些发现表明库普弗细胞保护肝细胞免受单核细胞增生李斯特菌感染和由此导致的细胞凋亡。此外，MIP-2及其由受感染的肝细胞产生的相关分子调节原发性李斯特菌病中的中性粒细胞浸润和微脓肿形成。
Depletion of mouse Kupffer cells and splenic macrophages following intravenous administration of liposome-entrapped clodronate severely reduced host resistance to primary infection with Listeria monocytogenes, Infection of clodronate-treated mice with a sublethal dose of L. monocytogenes resulted in death of the mice within 3 days. The macrophage depletion resulted in marked increases in bacterial growth in the liver and spleen, but not in other tissues. The proliferation of L. monocytogenes was observed in a large number of hepatocytes that underwent apoptosis. Infiltration of neutrophils in the liver and rapid formation of microabscesses were observed in the control mice after L. monocytogenes infection. However, there was less accumulation of neutrophils in the liver of Kupffer cell-depleted mice than in the control mice, Expression of macrophage inflammatory protein-2 (MIP-2) was enhanced in the livers of both the control and Kupffer cell-depleted mice after L. monocytogenes infection. MIP-2 was also induced in a murine hepatocyte cell line following L. monocytogenes infection. The administration of neutralizing anti-interleukin-8 receptor homolog antibody severely abrogated neutrophil infiltration into the Listeria-infected mouse liver, Anti-MIP-P antibody moderately reduced neutrophil infiltration and microabscess formation in the liver. These findings indicate that Kupffer cells protect hepatocytes from L. monocytogenes infection and the resultant apoptosis. Moreover, MIP-2 and its related molecules produced by the infected hepatocytes regulate neutrophil infiltration and microabscess formation in primary listeriosis.