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Resistin directly inhibits bacterial killing in neutrophils
Intensive Care Medicine Experimental Pub Date : 2019-05-30 , DOI: 10.1186/s40635-019-0257-y
Lauren Miller 1 , Kai Singbartl 2 , Zissis C Chroneos 3, 4 , Victor Ruiz-Velasco 1 , Charles H Lang 5, 6 , Anthony Bonavia 1
Affiliation  

BackgroundSepsis-induced immunosuppression is a key factor contributing to the morbidity and mortality of critically ill patients, and polymorphonuclear neutrophil dysfunction is believed to be a hallmark of this immunosuppression. Circulating myeloid cells produce the cytokine resistin (RETN), which has been associated with poor outcomes in sepsis/septic shock and can directly inhibit neutrophil function. We previously demonstrated that resistin caused a dose-dependent impairment in neutrophil migration, reactive oxygen species production, and bacterial clearance in neutrophil cell lines. However, the relative antimicrobial responses of other innate immune cells to Gram-positive and Gram-negative infections in the presence of elevated levels of resistin have not been evaluated. We hypothesized that resistin directly contributes to sepsis-induced immunosuppression by selectively targeting the neutrophil component of the innate cellular immune system. Thus, the goal of the present study was to compare the effect of resistin on bacterial killing using monocultures or co-cultures of monocyte and neutrophil cell lines, as well as to extend our findings to primary immune cells.ResultsOur results indicate that human resistin impairs the ability of neutrophils to kill the Gram-negative bacterium Pseudomonas aeruginosa and the Gram-positive bacterium Staphylococcus aureus. In contrast, with the exception of macrophages incubated with P. aeruginosa, resistin did not affect the ability of macrophages or monocytes to kill either Gram-positive or Gram-negative organisms. Furthermore, co-incubation of neutrophils with increasing proportions of monocytes did not enhance bacterial killing. Resistin blocked bactericidal activity through partial reduction of F-actin polymerization and suppression of the oxidative burst in neutrophils.ConclusionsOur studies indicate that resistin selectively impairs neutrophil bacterial killing. These findings further support the notion that resistin can mimic cell type-dependent immunosuppressive effects. This is consistent with its putative role in the pathogenesis of bacterial sepsis.

中文翻译:

抵抗素直接抑制嗜中性粒细胞中的细菌杀伤

背景脓毒症诱导的免疫抑制是导致危重患者发病率和死亡率的关键因素,多形核中性粒细胞功能障碍被认为是这种免疫抑制的标志。循环骨髓细胞产生细胞因子抵抗素 (RETN),它与败血症/败血性休克的不良结果有关,并可直接抑制中性粒细胞功能。我们以前证明抵抗素在中性粒细胞系中引起中性粒细胞迁移、活性氧产生和细菌清除的剂量依赖性损伤。然而,尚未评估其他先天免疫细胞在抵抗素水平升高的情况下对革兰氏阳性和革兰氏阴性感染的相对抗菌反应。我们假设抵抗素通过选择性靶向先天细胞免疫系统的中性粒细胞成分而直接导致败血症诱导的免疫抑制。因此,本研究的目标是使用单核细胞和中性粒细胞系的单培养或共培养来比较抵抗素对细菌杀伤的影响,并将我们的发现扩展到原代免疫细胞。结果我们的结果表明人类抵抗素会损害中性粒细胞杀死革兰氏阴性菌铜绿假单胞菌和革兰氏阳性菌金黄色葡萄球菌的能力。相比之下,除了与铜绿假单胞菌一起孵育的巨噬细胞外,抵抗素不影响巨噬细胞或单核细胞杀死革兰氏阳性或革兰氏阴性生物的能力。此外,中性粒细胞与单核细胞比例增加的共同培养不会增强细菌杀伤。抵抗素通过部分减少 F-肌动蛋白聚合和抑制中性粒细胞中的氧化爆发来阻断杀菌活性。结论我们的研究表明抵抗素选择性地削弱了对中性粒细胞的杀灭作用。这些发现进一步支持抵抗素可以模拟细胞类型依赖性免疫抑制作用的观点。这与其在细菌性败血症发病机制中的假定作用一致。这些发现进一步支持抵抗素可以模拟细胞类型依赖性免疫抑制作用的观点。这与其在细菌性败血症发病机制中的假定作用一致。这些发现进一步支持抵抗素可以模拟细胞类型依赖性免疫抑制作用的观点。这与其在细菌性败血症发病机制中的假定作用一致。
更新日期:2019-05-30
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