title: Human astrocytes inhibit Cryptococcus neoformans growth by a nitric oxide-mediated mechanism.
abstract: 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.
authors.affiliation: Department of Pathology Neuropathology, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.forename: D W
authors.initials: DW
authors.lastname: Dickson
authors.forename: C F
authors.initials: CF
authors.lastname: Brosnan
authors.forename: A
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000254:growth & development*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019323:omega-N-Methylarginine
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D007930:Leucine; D019331:NG-Nitroarginine Methyl Ester