Yamashita Kouhei, Miyoshi Takashi, Arai Toshiyuki, Endo Nobuyuki, Itoh Hiroshi, Makino Keisuke, Mizugishi Kiyomi, Uchiyama Takashi, Sasada Masataka
Departments of Hematology and Oncology and Anesthesia, Kyoto University Hospital, Kyoto 606-8507, Japan.
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16912-7. doi: 10.1073/pnas.0807952105. Epub 2008 Oct 29.
Reactive oxygen species produced by phagocytosing neutrophils are essential for innate host defense against invading microbes. Previous observations revealed that antibody-catalyzed ozone formation by human neutrophils contributed to the killing of bacteria. In this study, we discovered that 4 amino acids themselves were able to catalyze the production of an oxidant with the chemical signature of ozone from singlet oxygen in the water-oxidation pathway, at comparable level to antibodies. The resultant oxidant with the chemical signature of ozone exhibited significant bactericidal activity in our distinct cell-free system and in human neutrophils. The results also suggest that an oxidant with the chemical signature of ozone produced by neutrophils might potentiate a host defense system, when the host is challenged by high doses of infectious agents. Our findings provide biological insights into the killing of bacteria by neutrophils.
吞噬性中性粒细胞产生的活性氧物种对于宿主抵御入侵微生物的天然防御至关重要。先前的观察结果表明,人类中性粒细胞通过抗体催化形成臭氧有助于杀灭细菌。在本研究中,我们发现4种氨基酸自身能够在水氧化途径中催化从单线态氧产生具有臭氧化学特征的氧化剂,其水平与抗体相当。在我们独特的无细胞系统和人类中性粒细胞中,所产生的具有臭氧化学特征的氧化剂表现出显著的杀菌活性。结果还表明,当中性粒细胞产生的具有臭氧化学特征的氧化剂在宿主受到高剂量感染因子挑战时,可能会增强宿主防御系统。我们的研究结果为中性粒细胞杀灭细菌提供了生物学见解。