From the Department of Surgery, Wayne State University, Detroit, Michigan.
J Trauma Acute Care Surg. 2013 Dec;75(6):1047-51; discussion 1051-2. doi: 10.1097/TA.0b013e3182a1fec0.
Obesity is associated with a higher risk of remote organ failure after shock and trauma. The mechanism(s) is poorly understood. Polymorphonuclear cell (PMN) inflammatory responses are important in the pathogenesis of organ injury following shock. Morbid obesity is a low-grade inflammatory state associated with proinflammatory mediator production from adipose tissue. We hypothesized that adipose tissue may modulate PMN inflammatory potential and is dependent on the magnitude of the injury-related stress response. This was studied in an in vitro model.
Adipose-derived stem cells (ADSCs) conditioned to behave as mature adipocytes were incubated with physiologic and stress concentrations of adrenaline for 12 hours, and cell culture supernatants were obtained. PMNs from normal human volunteers were cocultured with the ADSC supernatants (priming) followed by addition of 1-μM fMLP (activation). PMNs alone served as control. PMN activation was indexed by superoxide anion (O2) production, elastase release (%) and CD11b expression (mean fluorescent intensity).
Physiologic and stress levels of adrenaline resulted in significantly increased PMN activation in the presence or absence of adipocytes. However, the largest increase was noted in PMNs exposed to ADSC culture supernatants that had been cocultured with stress levels of adrenaline for 12 hours, twofold increase in CD11b expression and fourfold increase in superoxide anion and percent elastase release.
Adipocyte-derived mediators prime PMNs in vitro. There was a graded PMN response to adrenaline concentration with or without adipocytes in these experiments. The most profound increase in PMN inflammatory potential was noted with the adipocyte supernatant + stress adrenaline group. The clinical impact of obesity on remote organ injury is likely dependent on patient body mass index and the injury-related sympathetic responses. These data suggest a potential role for β blockade in this patient population.
肥胖与休克和创伤后远程器官衰竭的风险增加有关。其机制尚不清楚。多形核细胞（PMN）炎症反应在休克后器官损伤的发病机制中很重要。病态肥胖是一种与脂肪组织产生促炎介质有关的低度炎症状态。我们假设脂肪组织可能调节 PMN 的炎症潜能，并且依赖于与损伤相关的应激反应的程度。这在体外模型中进行了研究。
将脂肪来源的干细胞（ADSCs）条件培养为成熟脂肪细胞，用生理和应激浓度的肾上腺素孵育 12 小时，然后获得细胞培养上清液。将正常人志愿者的 PMN 与 ADSC 上清液（预培养）共培养，然后加入 1μM fMLP（激活）。单独的 PMN 作为对照。PMN 激活的指标为超氧阴离子（O2）产生、弹性蛋白酶释放（%）和 CD11b 表达（平均荧光强度）。
生理和应激水平的肾上腺素导致 PMN 在存在或不存在脂肪细胞的情况下显著激活。然而，在与应激水平的肾上腺素共培养 12 小时的 ADSC 培养上清液中暴露的 PMN 中观察到最大的增加，CD11b 表达增加两倍，超氧阴离子和弹性蛋白酶释放增加四倍。
脂肪细胞衍生的介质在体外对 PMN 进行预培养。在这些实验中，无论是否存在脂肪细胞，肾上腺素浓度都与 PMN 呈梯度反应。在脂肪细胞上清液+应激肾上腺素组中，PMN 炎症潜能的增加最为显著。肥胖对远程器官损伤的临床影响可能取决于患者的体重指数和与损伤相关的交感神经反应。这些数据表明，β 阻断在这类患者人群中可能具有潜在作用。
