The down regulation of neutrophil oxidative metabolism by S100A8 and S100A9: implication of the protease-activated receptor-2.
The down regulation of neutrophil oxidative metabolism by S100A8 and S100A9: implication of the protease-activated receptor-2.
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DOI：
10.1016/j.molimm.2011.12.001
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发表时间：
2012-02
影响因子：
3.6
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Sroussi HY;Lu Y;Villines D;Sun Y
S100 A8和S100 A9调节多形核中性粒细胞（PMN）的募集，占PMN胞质蛋白质重量的40%。我们已经证明S100 A8/S100 A9抑制PMN氧化代谢。本研究旨在阐明这种抗氧化作用的机制。我们推测，蛋白酶激活受体-2（PAR-2）在S100 A8/S100 A9下调PMN氧化代谢中发挥作用。测试新鲜分离的中性粒细胞氧化二氯荧光素-二乙酸酯的能力。用ENMD-1068、pepducin P2pal-21或针对PAR-2切割/活化位点的抗体对PAR-2的功能性抑制导致S100 A8和S100 A9抗氧化作用的显著抑制。相反，PAR-2的受控激活增强了S100的抗氧化作用。综上所述，数据表明S100 A8/A9的抗氧化作用是由PAR-2活化引发的。因此，S100 A8/S100 A9可以抑制炎症，而不干扰其初始强度。这一发现开辟了通过双重PAR-2/S100策略限制有害中性粒细胞激活的翻译可能性。
S100A8 and S100A9 regulate polymorphonuclear neutrophils (PMNs) recruitment and represent 40% of PMN cytosolic protein weight. We have shown that S100A8/S100A9 inhibit PMN oxidative metabolism. The present study was designed to elucidate the mechanisms of this anti-oxidative effect. We hypothesized that the protease activated receptor-2 (PAR-2) played a role in the down-regulation of PMN oxidative metabolism by S100A8/S100A9. Freshly isolated PMNs were tested for their ability to oxidize dichlorofluorescin-diacetate. Functional inhibition of PAR-2 with ENMD-1068, the pepducin P2pal-21 or an antibody directed at PAR-2 cleavage/activation site, resulted in a significant inhibition of S100A8 and S100A9 anti-oxidative effect. Conversely, the controlled activation of PAR-2 potentiated S100 anti-oxidative effect. Taken together, the data indicate that the anti-oxidative effect of S100A8/A9 is initiated by PAR-2 activation. S100A8/S100A9 may therefore dampen inflammation without interfering with its initial strength. This finding opens translational possibilities to limit deleterious PMN activation with a dual PAR-2/S100 strategy.
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影响因子：
3
作者：
ECKERT, JW;ABRAMSON, SL;BRANDT, ML
通讯作者：
BRANDT, ML
DOI：
10.1046/j.1432-1033.2002.03002.x
发表时间：
2002-07-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Doussiere, J;Bouzidi, F;Vignais, PV
通讯作者：
Vignais, PV
影响因子：
3.1
作者：
Darveau, Richard P.
通讯作者：
Darveau, Richard P.
影响因子：
5
作者：
Kallenberg, Cees G M
通讯作者：
Kallenberg, Cees G M
影响因子：
3
作者：
Dale, CS;Gonçalves, LRC;Giorgi, R
通讯作者：
Giorgi, R