Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis
Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis
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DOI：
10.1097/01.ccm.0000295593.25106.c4
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发表时间：
2007-12-01
影响因子：
8.8
通讯作者：
Payen, Didier
中科院分区：
文献类型：
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作者：
Belikova, Ioulia;Lukaszewicz, Anne Claire;Payen, Didier
目的：脓毒症患者在初始刺激后，免疫细胞功能下调，进入免疫抑制状态。由于这种下调的机制尚不清楚，我们研究了免疫细胞能量衰竭参与免疫功能障碍的假设。设计：脓毒性休克患者队列研究外周血单个核细胞（PBMCs）生物能量与健康志愿者细胞的比较。环境：大学医院重症监护病房和实验室。研究对象：18例严重脓毒症或感染性休克患者和32名健康志愿者。干预措施：体外测量从患者身上采集的pbmc的耗氧量。采用二磷酸腺苷刺激法研究PBMCs线粒体氧化磷酸化。在脓毒症的不同时间点，使用在脓毒症血浆中孵育的健康细胞或在健康血浆中孵育的脓毒症细胞，对血浆因子的影响进行了测试。检测单核细胞人白细胞抗原dr表达与生物能量结果的关系。测量结果和主要结果：脓毒性PBMCs的基线耗氧量较高（p < 0.01），对二磷酸腺苷刺激的反应减弱（p < 0.01）。在脓毒症血浆中培养的健康pbmc的耗氧量模拟了脓毒症细胞的反应，其幅度取决于脓毒症的持续时间（0-28天）。在健康血浆中孵育的脓毒性细胞部分恢复正常模式。败血性血浆孵育增加解耦耗氧量的比例（p = 0.021）。在脓毒性休克的不同时间点采集血浆，观察氧消耗（基线或二磷酸腺苷刺激）与人白细胞抗原- dr表达的关系。结论：脓毒症患者外周血单核细胞的能量衰竭可能与免疫反应和人白细胞抗原- dr表型的调节有关，部分受血浆因素驱动。
Objective: During sepsis, after an initial stimulation immune cells down-regulate their functions, leading to a state of immunosuppression. Because the mechanisms of such down-regulation are unclear, we investigated the hypothesis of an energetic failure of immune cells to participate in immune dysfunction.Design: Cohort of septic shock patients to study peripheral blood mononuclear cells (PBMCs) biological energy in comparison to healthy volunteer cells.Setting: Critical care unit and laboratory, university hospital.Subjects: Eighteen severe sepsis or septic shock patients and 32 healthy volunteers.Interventions: Ex vivo measurement of oxygen consumption in PBMCs taken from patients. The PBMCs' mitochondrial oxidative phosphorylation was investigated using adenosine diphosphate stimulation. The plasma factors implication was tested, using healthy cells incubated in septic plasma, or septic cells incubated in healthy plasma, at different time points of sepsis. The relationship between monocyte human leukocyte antigen-DR expression and bioenergetic results was tested.Measurements and Main Results: Baseline oxygen consumption was higher in septic PBMCs (p < .01), with an attenuated response to adenosine diphosphate stimulation (p < .01). Oxygen consumption of healthy PBMCs incubated in septic plasma mimicked the septic cell response, with amplitude depending on the duration of sepsis (days 0-28). Septic cells incubated in healthy plasma partially recovered normal patterns. Septic plasma incubation increased the fraction of decoupling oxygen consumption (p = .021). A relationship between oxygen consumption (baseline or adenosine diphosphate stimulated) and human leukocyte antigen-DR expression was observed for incubation with plasma sampled at different time points of septic shock.Conclusion: Energetic failure of PBMCs in sepsis may be a factor associated with the modulation of immune response and human leukocyte antigen-DR phenotype, partially driven by plasma factors.