Substitution of methionine 63 or 83 in S100A9 and cysteine 42 in S100A8 abrogate the antifungal activities of S100A8/A9: potential role for oxidative regulation

被引:32
作者
Sroussi, Herve Y. [1 ]
Koehler, Gerwald A. [2 ,3 ]
Agabian, Nina [2 ]
Villines, Dana [1 ]
Palefsky, Joel M. [4 ]
机构
[1] Univ Illinois, Dept Oral Med & Diagnost Sci, UIC Coll Dent, Chicago, IL 60612 USA
[2] Univ Calif San Francisco, Sch Dent, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA
[3] Oklahoma State Univ, Ctr Hlth Sci, Dept Biochem & Microbiol, Tulsa, OK USA
[4] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA
来源
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY | 2009年 / 55卷 / 01期
关键词
Candida albicans; antifungal; calprotectin; S100A8; S100A9; oxidation; PROTEIN; CALPROTECTIN; MIGRATION;
D O I
10.1111/j.1574-695X.2008.00498.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
S100A8 and S100A9 and their heterocomplex calprotectin (S100A8/A9) are abundant cytosolic constituents in human neutrophils previously shown to possess antifungal activity. This study was designed to investigate mechanisms involved in the modulation of the antifungal properties of S100A8/A9. S100A8, S100A9 and site-directed mutants of both proteins were tested for their antifungal effect against Candida albicans in microplate dilution assays. Whereas S100A8 alone did not inhibit fungal growth, S100A9 by itself had a moderate antifungal effect. Combining both proteins had the strongest effect. Supporting a potential role for oxidation in S100A8/A9, substitution of methionine 63 or 83 of S100A9 resulted in the loss of antifungal activity. Additionally, the substitution to alanine of cysteine 42 of S100A8 also caused a loss of S100A8's ability to enhance S100A9's antifungal effect. Overall, our data indicate that both S100A8 and S100A9 are required for their fully active antifungal effect and that oxidation regulates S100A8/A9 antifungal activity through mechanisms that remain to be elucidated and evaluated. Finally, together with our previous work describing the oxidation-sensitive anti-inflammatory effects of S100A8/A9, we propose that S100A8/A9 exerts an anti-inflammatory activity in healthy state and that conditions associated with oxidative stress activate the antifungal activity of S100A8/A9.
引用
收藏
页码:55 / 61
页数:7
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