<br>CD206 的腹膜水平与失代偿期肝硬化和自发性细菌性腹膜炎患者的死亡率和炎性巨噬细胞表型相关。,Gastroenterology

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CD206 的腹膜水平与失代偿期肝硬化和自发性细菌性腹膜炎患者的死亡率和炎性巨噬细胞表型相关。
Gastroenterology ( IF 25.7 ) Pub Date : 2020-01-23 , DOI: 10.1053/j.gastro.2020.01.029
Sven Stengel ₁ , Stefanie Quickert ₁ , Philipp Lutz ₂ , Oluwatomi Ibidapo-Obe ₁ , Arndt Steube ₁ , Nilay Köse-Vogel ₁ , Melina Yarbakht ₃ , Philipp A Reuken ₁ , Martin Busch ₄ , Annette Brandt ₅ , Ina Bergheim ₅ , Sachin D Deshmukh ₆ , Andreas Stallmach ₁ , Tony Bruns ₇

Affiliation

Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany.
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, University of Bonn, Bonn, Germany.
Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany; The Integrated Research and Treatment Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
Department of Internal Medicine III, Jena University Hospital, Jena, Germany.
Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria.
The Integrated Research and Treatment Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany; The Integrated Research and Treatment Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Department of Internal Medicine III, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.

背景和目标腹膜巨噬细胞（PMs）调节炎症并控制失代偿性肝硬化患者的细菌感染。我们旨在表征 PM 并将其激活与自发性细菌性腹膜炎（SBP）患者的结局相关联。方法我们从 66 例失代偿性肝硬化患者（19 例 SBP）的腹水中样本中分离出 PM，并通过流式细胞术、定量实时聚合酶链反应、功能分析和 RNA 微阵列对其进行分析。我们使用了 111 名失代偿性肝硬化患者（67 名 SBP）的单独队列的腹水样本，并通过酶联免疫吸附测定（测试队列）量化了甘露糖受体（CD206）和肿瘤坏死因子的可溶性形式。我们进行了 logistic 回归分析以确定与 90 天死亡率相关的因素。我们使用 71 例肝硬化和 SBP 患者的数据验证了我们的发现。来自 14 例因终末期肾病接受腹膜透析但无肝硬化的患者的数据作为对照。结果我们使用 CD206 的表层水平来识别肝硬化患者腹水样本中大 PM （LPM）和小 PM （SPM）的亚群，它们在粒度和成熟标志物上有所不同。肝硬化患者的 LPMs 与 SPMs 具有不同的转录组;我们鉴定了 4000 多个在 LPMs 与 SPM 中受到差异调控的基因，包括调节周期、代谢、自我更新和免疫细胞信号传导的基因。LPMs 具有炎症表型，对耐受性诱导的敏感性较低，并且比 SPM 释放更多的肿瘤坏死因子。肝硬化患者的 LPMs 比对照组的 LPM 产生更多的炎性细胞因子。 Toll 样受体激动剂和活细菌激活 PM 改变了 LPM 表面 CD206 的水平并释放了可溶性 CD206。对 SBP 患者连续腹水的分析显示 LPM 在 SBP 早期丢失，但治疗后水平升高。在测试和验证队列中，腹水中可溶性 CD206 浓度较高（>0.53 mg/L）的 SBP 患者比水平较低的患者存活 90 天的可能性更小。结论 CD206 表层可用于识别肝硬化患者成熟、常驻、炎症性 PM。可溶性 CD206 从活化的 LPM 中释放出来，肝硬化和 SBP 患者的浓度增加表明 90 天存活的几率降低。

"点击查看英文标题和摘要"

Peritoneal Level of CD206 Associates With Mortality and an Inflammatory Macrophage Phenotype in Patients With Decompensated Cirrhosis and Spontaneous Bacterial Peritonitis.

BACKGROUND & AIMS Peritoneal macrophages (PMs) regulate inflammation and control bacterial infections in patients with decompensated cirrhosis. We aimed to characterize PMs and associate their activation with outcomes of patients with spontaneous bacterial peritonitis (SBP). METHODS We isolated PMs from ascites samples of 66 patients with decompensated cirrhosis (19 with SBP) and analyzed them by flow cytometry, quantitative real-time polymerase chain reaction, functional analysis, and RNA microarrays. We used ascites samples of a separate cohort of 111 patients with decompensated cirrhosis (67 with SBP) and quantified the soluble form of the mannose receptor (CD206) and tumor necrosis factor by enzyme-linked immunosorbent assay (test cohort). We performed logistic regression analysis to identify factors associated with 90-day mortality. We validated our findings using data from 71 patients with cirrhosis and SBP. Data from 14 patients undergoing peritoneal dialysis for end-stage renal disease but without cirrhosis were included as controls. RESULTS We used surface levels of CD206 to identify subsets of large PMs (LPM) and small PMs (SPM), which differed in granularity and maturation markers, in ascites samples from patients with cirrhosis. LPMs vs SPMs from patients with cirrhosis had different transcriptomes; we identified more than 4000 genes that were differentially regulated in LPMs vs SPMs, including those that regulate the cycle, metabolism, self-renewal, and immune cell signaling. LPMs had an inflammatory phenotype, were less susceptible to tolerance induction, and released more tumor necrosis factor than SPMs. LPMs from patients with cirrhosis produced more inflammatory cytokines than LPMs from controls. Activation of PMs by Toll-like receptor agonists and live bacteria altered levels of CD206 on the surface of LPMs and release of soluble CD206. Analysis of serial ascites fluid from patients with SBP revealed loss of LPMs in the early phase of SBP, but levels increased after treatment. In the test and validation cohorts, patients with SBP and higher concentrations of soluble CD206 in ascites fluid (>0.53 mg/L) were less likely to survive for 90 days than those with lower levels. CONCLUSIONS Surface level of CD206 can be used to identify mature, resident, inflammatory PMs in patients with cirrhosis. Soluble CD206 is released from activated LPMs and increased concentrations in patients with cirrhosis and SBP indicate reduced odds of surviving for 90 days.

更新日期：2020-01-23

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