Lee S C, Dickson D W, Brosnan C F, Casadevall A
Department of Pathology Neuropathology, Albert Einstein College of Medicine, Bronx, New York 10461.
J Exp Med. 1994 Jul 1;180(1):365-9. doi: 10.1084/jem.180.1.365.
Cryptococcus neoformans is an opportunistic fungus that causes life-threatening meningoencephalitis in 5-10% of patients with acquired immune deficiency syndrome. Cryptococcal meningoencephalitis is characterized by a lymphohistiocytic infiltrate, accumulation of encapsulated forms of C. neoformans, and varying degrees of glial reaction. Little is known about the contribution of endogenous central nervous system cells to the pathogenesis of cryptococcal infections. In this study, we investigated the role of astrocytes as potential effector cells against C. neoformans. Primary cultures of human fetal astrocytes, activated with interleukin 1 beta plus interferon gamma inhibited the growth of C. neoformans. The inhibition of C. neoformans growth was paralleled by production of nitrite, and reversed by the inhibitors of nitric oxide (NO.) synthase, NG-methyl-mono-arginine and NG-nitro-arginine methyl ester. The results suggest a novel function for human astrocytes in host defence and provide a precedent for the use of NO. as an antimicrobial effector molecule by human cells.
新型隐球菌是一种机会性真菌，在5%至10%的获得性免疫缺陷综合征患者中可引起危及生命的脑膜脑炎。隐球菌性脑膜脑炎的特征是淋巴细胞-组织细胞浸润、新型隐球菌荚膜形式的积聚以及不同程度的胶质反应。关于内源性中枢神经系统细胞在隐球菌感染发病机制中的作用知之甚少。在本研究中，我们调查了星形胶质细胞作为抗新型隐球菌潜在效应细胞的作用。用人白细胞介素1β加干扰素γ激活的人胎儿星形胶质细胞原代培养物可抑制新型隐球菌的生长。新型隐球菌生长的抑制与亚硝酸盐的产生平行，并被一氧化氮（NO.）合酶抑制剂NG-甲基-单-精氨酸和NG-硝基-精氨酸甲酯逆转。这些结果提示了人星形胶质细胞在宿主防御中的新功能，并为人类细胞将NO.用作抗菌效应分子提供了先例。
