Wang W, Keller K, Chadee K
Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Québec, Canada.
Infect Immun. 1992 Aug;60(8):3169-74. doi: 10.1128/iai.60.8.3169-3174.1992.
The macrophage-derived mediator tumor necrosis factor alpha (TNF) is a cytokine with pleiotropic effects. TNF exhibits potent immunologic and inflammatory properties in parasitic diseases. The present study examined the production of TNF by macrophages isolated from gerbils infected with Entamoeba histolytica and by naive macrophages in response to amoebae in vitro. Amoebic liver abscess-derived macrophages produced low constitutive basal levels of TNF; in response to lipopolysaccharide (LPS) stimulation, TNF production was enhanced by 14-, 11-, and 6-fold at 10, 20, and 30 days postinfection, respectively. Amoebic liver abscess-derived macrophages pretreated with either recombinant gamma interferon (IFN-gamma) or the cyclooxygenase inhibitor indomethacin augmented TNF production in response to soluble amoebic proteins and LPS. Kupffer cells and peritoneal and spleen macrophages from infected animals did not release TNF constitutively in vitro. However, TNF production in response to LPS stimulation was significantly higher at 10 and 20 days postinfection. Macrophages from infected and naive animals pretreated with recombinant IFN-gamma or indomethacin produced increased amounts of TNF in response to LPS but not in response to soluble amoebic protein stimulation. Pretreatment of naive macrophages with amoebic proteins inhibited LPS-induced TNF production by 69 to 79%; the effect of the amoebic proteins was partially reversed by indomethacin pretreatment. In contrast, IFN-gamma- and LPS-activated naive macrophages produced enhanced levels of TNF in response to live amoebae and soluble amoebic proteins. Our results demonstrate that TNF production by macrophages is altered during E. histolytica infection and in response to amoebae and suggest a role for IFN-gamma and prostaglandin E2 in regulating TNF production during the infection.
巨噬细胞衍生的介质肿瘤坏死因子α（TNF）是一种具有多效性的细胞因子。TNF在寄生虫病中表现出强大的免疫和炎症特性。本研究检测了从感染溶组织内阿米巴的沙鼠中分离出的巨噬细胞以及体外对阿米巴作出反应的未感染巨噬细胞产生TNF的情况。阿米巴肝脓肿来源的巨噬细胞产生的TNF基础组成水平较低；在脂多糖（LPS）刺激下，感染后10、20和30天TNF的产生分别增加了14倍、11倍和6倍。用重组γ干扰素（IFN-γ）或环氧化酶抑制剂吲哚美辛预处理的阿米巴肝脓肿来源的巨噬细胞，对可溶性阿米巴蛋白和LPS作出反应时TNF产生增加。感染动物的库普弗细胞、腹膜巨噬细胞和脾巨噬细胞在体外不组成性释放TNF。然而，感染后10天和20天，对LPS刺激的TNF产生显著更高。用重组IFN-γ或吲哚美辛预处理的感染和未感染动物的巨噬细胞，对LPS作出反应时产生的TNF量增加，但对可溶性阿米巴蛋白刺激无反应。用阿米巴蛋白预处理未感染巨噬细胞可使LPS诱导的TNF产生减少69%至79%；吲哚美辛预处理可部分逆转阿米巴蛋白的作用。相比之下，IFN-γ和LPS激活的未感染巨噬细胞对活阿米巴和可溶性阿米巴蛋白作出反应时产生的TNF水平升高。我们的结果表明，巨噬细胞产生TNF在溶组织内阿米巴感染期间以及对阿米巴的反应中发生改变，并提示IFN-γ和前列腺素E2在感染期间调节TNF产生中起作用。
