期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 192, 期 2, 页码 227-236出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.2.227
关键词
phagocyte; Salmonella; innate immunity; nitrosative; oxidative
资金
- NIAID NIH HHS [F32 AI010181, AI44486, R01 AI044486, R01 AI039557, AI10181, AI39557] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
The contribution of the NADPH phagocyte oxidase (phox) and inducible nitric oxide (NO) synthase (iNOS) to the antimicrobial activity of macrophages for Salmonella typhimurium was studied by using peritoneal phagocytes from C57BL/6, congenic gp91phox(-/-), iNOS(-/-), and doubly immunodeficient phox(-/-)iNOS(-/-) mice. The respiratory burst and NO radical (NO) made distinct contributions to the anti-Salmonella activity of macrophages. NADPH oxidase-dependent killing is confined to the first few hours after phagocytosis, whereas iNOS contributes to both early and late phases of antibacterial activity. NO-derived species initially synergize with oxyradicals to kill S. typhimurium, and subsequently exert prolonged oxidase-independent bacteriostatic effects. Biochemical analyses show that early killing of Salmonella by macrophages coincides with an oxidative chemistry characterized by superoxide anion (O-2.(-)), hydrogen peroxide (H2O2), and peroxynitrite (ONOO-) production. However, immunofluorescence microscopy and killing assays using the scavenger uric acid suggest that peroxynitrite is not responsible for macrophage killing of wild-type S. typhimurium. Rapid oxidative bacterial killing is followed by a sustained period of nitrosative chemistry that limits bacterial growth. Interferon gamma appears to augment antibacterial activity predominantly by enhancing NO . production, although a small iNOS-independent effect was also observed. These findings demonstrate that macrophages kill Salmonella in a dynamic process that changes over time and requires the generation of both reactive oxidative and nitrosative species.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据