Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model.
Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model.
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DOI：
10.3390/antiox10111676
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发表时间：
2021-10-24
期刊：
影响因子：
--
通讯作者：
Chatterjee S
中科院分区：
文献类型：
--
作者：
Fisher AB;Dodia C;Tao JQ;Feinstein SI;Chatterjee S
已经提出使用抑制活性氧（ROS）产生的试剂来治疗急性肺损伤（ALI）。然而，这种方法也抑制了多形核白细胞（PMN）和其他细胞的杀菌活性，增加了加重与细菌感染相关的ALI肺损伤的可能性。我们采用盲肠结扎穿孔（CLP）脓毒症相关ALI模型，研究抑制NADPH氧化酶2（NOX 2）衍生的ROS产生（肺中ROS的主要来源）的作用。使用称为过氧化物氧还蛋白6抑制肽-2（PIP-2）的磷脂酶A2抑制剂来抑制N 0X 2活化;所述肽阻止Rac（一种必需的N 0X 2辅因子）的释放。在用2 μg PIP-2 /克体重（wt）静脉内治疗后18小时，与未治疗的小鼠相比，患有CLP的小鼠的肺和腹膜液中的菌落形成细菌的数量大约加倍。10 µg PIP-2/g体重给药导致18 h内100%死亡率。抗生素治疗消除了低剂量PIP-2的肺细菌增加和高剂量PIP-2的死亡率增加。与单独使用抗生素相比，PIP-2加抗生素治疗导致肺组织学显著改善，PMN浸润减少，肺液体积聚减少，氧化性肺损伤减少。我们的结论是，PIP-2的管理提供了部分保护，对肺损伤的模型，由于细菌感染，而并发抗生素治疗废除了有害的影响，PIP-2对肺部细菌清除。这些结果表明，在抗生素方案中加入PIP-2对治疗与细菌感染相关的ALI有益。
The use of agents to inhibit the production of reactive oxygen species (ROS) has been proposed for the treatment of Acute Lung Injury (ALI). However, this approach also inhibits the bactericidal activity of polymorphonuclear leucocytes (PMN) and other cells, raising the possibility of aggravating lung injury in ALI associated with bacterial infection. We used the cecal ligation and puncture (CLP) model of ALI associated with sepsis to investigate the effect of inhibiting NADPH oxidase 2 (NOX2)-derived ROS production, the main source of ROS in lungs. A phospholipase A2 inhibitor called peroxiredoxin 6 inhibitory peptide-2 (PIP-2) was used to inhibit NOX2 activation; the peptide prevents liberation of Rac, a necessary NOX2 co-factor. At 18 h after intravenous treatment with 2 µg PIP-2 /gram body weight (wt), the number of colony-forming bacteria in lungs and peritoneal fluid of mice with CLP was approximately doubled as compared to untreated mice. Treatment with 10 µg PIP-2/g body wt resulted in 100% mortality within 18 h. Antibiotic treatment abolished both the increase in lung bacteria with low dose PIP-2 and the increased mortality with high dose PIP-2. Treatment with PIP-2 plus antibiotics resulted in significantly improved lung histology, decreased PMN infiltration, decreased lung fluid accumulation, and decreased oxidative lung injury compared to antibiotics alone. We conclude that the administration of PIP-2 provides partial protection against lung injury in a model of ALI due to bacterial infection, while concurrent antibiotic treatment abolishes the deleterious effects of PIP-2 on lung bacterial clearance. These results suggest that addition of PIP-2 to the antibiotic regimen is beneficial for treatment of ALI associated with bacterial infection.
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DOI：
10.3390/antiox10060925
发表时间：
2021-06-07
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Fisher AB;Dodia C;Chatterjee S
通讯作者：
Chatterjee S
影响因子：
4.8
作者：
Chatterjee, Shampa;Feinstein, Sheldon I.;Fisher, Aron B.
通讯作者：
Fisher, Aron B.
影响因子：
--
作者：
FISHER, AB;DODIA, C;CHANDER, A
通讯作者：
CHANDER, A
DOI：
10.1016/j.bbamcr.2011.11.014
发表时间：
2012-02-01
影响因子：
5.1
作者：
Ambruso, Daniel R.;Ellison, Michael A.;Leto, Thomas L.
通讯作者：
Leto, Thomas L.
影响因子：
5.6
作者：
Abdelmageed, Marwa E.;El-Awady, Mohammed S.;Suddek, Ghada M.
通讯作者：
Suddek, Ghada M.