The anti-oxidative, anti-inflammatory, and protective effect of S100A8 in endotoxemic mice.
The anti-oxidative, anti-inflammatory, and protective effect of S100A8 in endotoxemic mice.
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DOI：
10.1016/j.molimm.2012.10.002
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发表时间：
2013-04
影响因子：
3.6
通讯作者：
Sroussi HY
中科院分区：
文献类型：
--
作者：
Sun Y;Lu Y;Engeland CG;Gordon SC;Sroussi HY
多形核中性粒细胞（PMN）产生并释放大量活性氧（ROS），这些活性氧是潜在细菌入侵者的目标，但也会导致脓毒症中与炎症相关的器官损伤。钙卫蛋白是一种由 S100A8 和 S100A9 组成的免疫调节蛋白复合物，可在体外抑制中性粒细胞的氧化代谢，这种作用可通过蛋白酶激活受体 2 (PAR2) 的受控激活来增强。本研究的目的是测试使用钙卫蛋白和 PAR2 双重给药策略来减轻脓毒症中的有害炎症。我们假设外源性钙卫蛋白可以防止脂多糖 (LPS) 诱导的内毒素血症造成的损伤，并且 PAR2 的受控激活将增强这种有益作用。在LPS诱导的内毒素血症小鼠模型中施用外源S100A8和/或PAR2激活肽(PAR2 AP)。测量了内毒素血症小鼠的肺、肾和肝脏的存活率以及炎症和氧化损伤标志物。 LPS后用S100A8治疗的小鼠的PMN浸润较少，肺、肾和肝的组织学变化也较轻。与单独用 LPS 治疗的小鼠相比，S100A8/LPS 治疗的小鼠肝脏和肺部的氧化损伤得分显着降低。 S100A8 的这种保护和抗炎作用通过 PAR2 的受控激活得到增强。最后，进一步支持我们的假设，分别接受 S100A8 和 PAR2 AP 治疗的小鼠的存活率几乎翻倍，从 33% 分别达到 65% 和 63%，而同时接受 PAR2 AP 和 S100A8 治疗的小鼠有 85% 的存活率，统计上显着更高。这些结果支持 S100A8 在脓毒症中的抗炎、抗氧化和保护作用，并值得进一步研究 PAR2 的作用。
Polymorphonuclear neutrophils (PMNs) produce and release copious amounts of reactive oxygen species (ROS) which target potential bacterial invaders but also contribute to the inflammation-associated organ injuries seen in sepsis. Calprotectin is an immune regulatory protein complex made of S100A8 and S100A9 that inhibits the oxidative metabolism of PMNs in vitro, an effect that can be potentiated by the controlled activation of the protease activated receptor-2 (PAR2). The aim of this study was to test the use of a dual strategy of calprotectin and PAR2 administration to mitigate the deleterious inflammation seen in sepsis. We hypothesized that exogenous calprotectin would protect against the injuries produced by lipopolysaccharides (LPS)-induced endotoxemia and that the controlled activation of PAR2 would potentiate this beneficial effect. Exogenous S100A8 and/or a PAR2 activating peptide (PAR2 AP) were administered in a mouse model of LPS induced endotoxemia. The survival rates as well as markers of inflammation and oxidative damage were measured in the lungs, kidneys, and livers of endotoxemic mice. Mice treated with S100A8 following LPS had less PMN infiltration and less severe histological changes in their lungs, kidneys, and livers. A significantly lower score of oxidative damage in the livers and lungs of S100A8/LPS treated mice was also noted when compared to mice treated with LPS alone. This protective and anti-inflammatory effect of S100A8 was potentiated by the controlled activation of PAR2. Finally, in further support to our hypothesis, the survival rate was almost doubled from 33% to 65% and 63% in mice treated by, respectively, S100A8 and PAR2 AP, whereas 85% of the mice treated with both PAR2 AP and S100A8 survived, a statistically significant higher rate. These results support an anti-inflammatory, anti-oxidative, and protective effect of S100A8 in sepsis, and warrant further studies on the role of PAR2.
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DOI：
10.1097/ta.0b013e3181dbb289
发表时间：
2010-12-01
影响因子：
--
作者：
Guerreiro, Marcio Osorio;Petronilho, Fabricia;Ritter, Cristiane
通讯作者：
Ritter, Cristiane
影响因子：
6.4
作者：
Marshall, JC;Foster, D;Romaschin, A
通讯作者：
Romaschin, A
影响因子：
2.2
作者：
Molnar, RG;Wang, P;Chaudry, IH
通讯作者：
Chaudry, IH
影响因子：
5
作者：
Kallenberg, Cees G M
通讯作者：
Kallenberg, Cees G M
影响因子：
4.4
作者：
Lindner, JR;Kahn, ML;Ley, K
通讯作者：
Ley, K