Peroxynitrite contributes to the candidacidal activity of nitric oxide-producing macrophages.
Peroxynitrite contributes to the candidacidal activity of nitric oxide-producing macrophages.
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过氧亚硝酸盐有助于产生一氧化氮的巨噬细胞的念珠菌活性。
DOI：
10.1128/iai.64.8.3127-3133.1996
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发表时间：
1996
影响因子：
3.1
通讯作者：
Balish,E
中科院分区：
文献类型：
--
作者：
Vazquez-Torres,A;Jones-Carson,J;Balish,E
一氧化氮（NO）与多种功能相关，如血管扩张、血流、神经内分泌、视觉传导、平滑肌松弛和微生物杀灭（H。H. W. H.施密特和V. Walter，Cell 78：919-925，1994）。尽管NO在巨噬细胞杀念珠菌活性中的作用已经得到了很好的证实（E.琴奇湖Romani，A.曼卡奇河Spaccapelo，E. Schiaffella，P. Puccetti，and F.比斯托尼，欧洲23：1034-1038，1993; J. Jones-Carson，A. Vazquez-Torres，H.货车德海德河D.瓦格纳，T. Warner和E. Balish，Nature Med.1：552-557，1995;和A.作者：J. Warner和E. Balish，J. Infect. 172：192-198，1995），NO不直接杀白色念珠菌（A. Vazquez-Torres、J. Jones-Carson和E. Balish，Infect. Immun. 63：1142-1144，1995）。由于巨噬细胞可以产生NO和超氧阴离子（O2-），我们假设过氧亚硝酸盐（ONOO-），NO和O2-的稀释限制反应的产物，是活化的巨噬细胞的杀念珠菌分子。我们现在报道，ONOO-，除了在体外杀念珠菌，是负责的杀念珠菌活性的NO产生的巨噬细胞。由NO产生巨噬细胞的ONOO-合成由两种独立的机制触发：一种是非调理素的，依赖于真菌细胞壁葡聚糖部分，另一种是依赖于调理素抗体。正如我们已经证明的致病真菌C。ONOO-也可能是使巨噬细胞能够杀死对O2-和NO都有抗性的其他微生物的分子。
Nitric oxide (NO) is associated with functions as diverse as peristalsis, blood flow, neuroendosecretion, visual transduction, smooth muscle relaxation, and microbial killing (H. H. W. H. Schmidt and V. Walter, Cell 78:919-925, 1994). Despite the well-established role of NO in macrophage candidacidal activity (E. Cenci, L. Romani, A. Mancacci, R. Spaccapelo, E. Schiaffella, P. Puccetti, and F. Bistoni, Eur. J. Immunol. 23:1034-1038, 1993; J. Jones-Carson, A. Vazquez-Torres, H. Van der Heide, R. D. Wagner, T. Warner, and E. Balish, Nature Med. 1:552-557, 1995; and A. Vazquez-Torres, J. Jones-Carson, T. Warner, and E. Balish, J. Infect. Dis. 172:192-198, 1995), NO is not directly candidacidal for Candida albicans (A. Vazquez-Torres, J. Jones-Carson, and E. Balish, Infect. Immun. 63:1142-1144, 1995). Because macrophages can produce both NO and superoxide anion (02-), we postulated that peroxynitrite (ONOO-), a product of the dilution-limited reaction of NO and O2-, is the candidacidal molecule of activated macrophages. We now report that ONOO-, in addition to being candidacidal in vitro, is responsible for the candidacidal activity of NO-producing macrophages. ONOO- synthesis by NO-producing macrophages was triggered by two independent mechanisms: one was nonopsonic and dependent on fungal cell wall glucan moieties, and the other was dependent on opsonic antibodies. As we have demonstrated for the pathogenic fungus C. albicans, ONOO- may also be the molecule that enables macrophages to kill other microbes that are resistant to both O2- and NO.