Schinkel C, Sendtner R, Zimmer S, Faist E
Ludwig-Maximilians University Munich, Klinikum Grosshadern, Department of Surgery, Germany.
J Trauma. 1998 May;44(5):743-8; discussion 748-9. doi: 10.1097/00005373-199805000-00001.
Sepsis still remains a major cause of death after surgery. Impaired monocyte (Mphi) function and disruption of monocyte (Mphi/T-cell interaction were shown to be crucial for the development of septic complications in these patients. It was the objective of the study to assess more insights in Mphi behavior in surgical sepsis by means of analysis of Fc receptor- and human leukocyte antigen DR (HLA-DR) expression in Mphi subsets, and to evaluate the kinetics of these changes.
In a prospective study, 20 septic patients and 10 healthy control subjects were included. Peripheral Mphi were isolated on consecutive days after onset of sepsis, and FcR positive (FcR+) and negative (FcR-) subsets were separated by rosetting with antibody-coated human erythrocytes. Cell surface receptor expression and in vitro cytokine production were used to determine the clinical importance of these subsets.
A significant monocytosis (3.5-fold; p < 0.01) and suppression of HLA-DR receptor expression (35%, p < 0.01) which correlate with sepsis severity and outcome could be demonstrated. There was a significant increase of FcR+ subsets in sepsis compared with control subjects (60% vs. 24%; p < 0.05). In vitro stimulation of Mphi subsets and peripheral blood mononuclear cells revealed suppressed interferon-gamma synthesis (p < 0.05 up to 0.01) from day 1 to day 5, elevated neopterin release (p < 0.05) on day 14 and increased synthesis rates of proinflammatory cytokines (e.g., interleukin-1beta); p < 0.05) predominantly in FcR+ subsets.
Sepsis results in a significant monocytosis and suppression of HLA-DR receptor expression, which are correlating with sepsis severity and outcome. A significant shift toward FcR+ Mphi subsets can be found. This subpopulation resembles the previously described "angry macrophage" that is characterized by high proinflammatory cytokine synthesis and suppressed antigen presentation and that contributes to a disruption of adequate Mphi/T-cell interaction, rendering the host anergic toward opportunistic infections. The extend of HLA-DR suppression and the shift toward FcR+ Mphi might characterize a high risk patient subpopulation, which could benefit from immunomodulatory strategies.
脓毒症仍是术后主要的死亡原因。单核细胞（Mphi）功能受损以及单核细胞（Mphi）/T细胞相互作用的破坏对这些患者脓毒症并发症的发生发展至关重要。本研究的目的是通过分析Mphi亚群中Fc受体和人类白细胞抗原DR（HLA-DR）的表达，进一步深入了解手术脓毒症中Mphi的行为，并评估这些变化的动力学。
在一项前瞻性研究中，纳入了20例脓毒症患者和10例健康对照者。在脓毒症发作后的连续几天分离外周血Mphi，通过与抗体包被的人类红细胞进行玫瑰花结试验分离FcR阳性（FcR+）和阴性（FcR-）亚群。利用细胞表面受体表达和体外细胞因子产生来确定这些亚群的临床重要性。
可证明存在显著的单核细胞增多（3.5倍；p<0.01）以及HLA-DR受体表达受抑制（35%，p<0.01），这与脓毒症的严重程度和预后相关。与对照者相比，脓毒症患者中FcR+亚群显著增加（60%对24%；p<0.05）。体外刺激Mphi亚群和外周血单个核细胞显示，从第1天到第5天干扰素-γ合成受抑制（p<0.05至0.01），第14天新蝶呤释放增加（p<0.05），促炎细胞因子（如白细胞介素-1β）的合成率增加（p<0.05），主要发生在FcR+亚群中。
脓毒症导致显著的单核细胞增多和HLA-DR受体表达受抑制，这与脓毒症的严重程度和预后相关。可发现向FcR+ Mphi亚群的显著转变。该亚群类似于先前描述的“愤怒巨噬细胞”，其特征是促炎细胞因子合成高且抗原呈递受抑制，导致适当的Mphi/T细胞相互作用破坏，使宿主对机会性感染无反应。HLA-DR抑制程度和向FcR+ Mphi的转变可能是高风险患者亚群的特征，这些患者可能从免疫调节策略中获益。
