高密度脂蛋白（HDL）中前表面活性蛋白B（pro-SFTPB）增加会促进HDL的促炎转变，这是急性呼吸窘迫综合征（ARDS）患者预后不良的一个迹象。

Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients.

作者信息

Yang Liu, Xu Zhuo, Wang Zhenyan, Ding Fangping, Wu Zhipeng, Shi Xiaoqian, Wang Jing, Ma Yingmin, Jin Jiawei

机构信息

Department of Respiratory and Critical Care Medicine, Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No.8 Xi Tou Tiao, Youanmen Wai, Beijing, China.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, N0.5 Jingyuan Road, Beijing, China.

出版信息

J Transl Med. 2025 Jan 16;23(1):75. doi: 10.1186/s12967-025-06100-6.

DOI:10.1186/s12967-025-06100-6

PMID:39819672

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11740663/

Abstract

BACKGROUND

Acute respiratory distress syndrome (ARDS) is causatively associated with excessive alveolar inflammation involving deregulated pro-inflammatory macrophage polarization. High-density lipoprotein (HDL) showed critical anti-inflammatory roles by modulating macrophage function, and its adverse transition to pro-inflammation has an important role in the pathogenesis of ARDS. However, the relationship between HDL protein constituents and functional remodeling is unknown in ARDS.

METHODS

Proteomic techniques were applied to examine the protein profile changes in HDL from septic-ARDS patients versus HDL from healthy controls across two distinct cohorts: a discovery cohort (8 patients and 8 healthy controls) and a validation cohort (22 patients and 10 healthy controls). The changed components significantly associated with prognosis were identified. Luminex assessed the levels of 38 plasma cytokines and chemokines. The in vitro constructed pro-SFTPB enriched HDL was applied to confirm the effect on M1 polarization of THP1-derived macrophage.

RESULTS

18 proteins were validated from 102 changed HDL proteins identified in the discovery cohort, including HDL particle components, such as apolipoproteins, pro-inflammatory substances known as serum amyloid As (SAAs), and anti-oxidative proteins like paraoxonases (PONs). Among these proteins, only the increase of pro-SFTPB in HDL was significantly associated with poor prognosis of ARDS patients. Notably, HDL-pro-SFTPB level was correlated with plasma pro-inflammatory cytokines and chemokines levels. The correlation assay of pro-SFTPB with other HDL components showed that it was positively and negatively correlated with SAA2 and PON3, respectively. Furthermore, the in vitro studies confirmed that the pro-SFTPB enriched HDL significantly promoted M1 polarization of monocyte-derived macrophages.

CONCLUSIONS

The increase of HDL-pro-SFTPB promotes HDL pro-inflammatory transition during septic ARDS, leading to exacerbated progression of ARDS through enhancing M1 macrophage polarization. HDL-pro-SFTPB could be a useful prognostic biomarker for septic ARDS.

摘要

背景

急性呼吸窘迫综合征（ARDS）与肺泡过度炎症相关，涉及促炎巨噬细胞极化失调。高密度脂蛋白（HDL）通过调节巨噬细胞功能发挥关键的抗炎作用，其向促炎状态的不良转变在ARDS发病机制中起重要作用。然而，ARDS中HDL蛋白成分与功能重塑之间的关系尚不清楚。

方法

应用蛋白质组学技术检测两个不同队列中脓毒症ARDS患者的HDL与健康对照者的HDL的蛋白质谱变化：一个发现队列（8例患者和8名健康对照）和一个验证队列（22例患者和10名健康对照）。鉴定出与预后显著相关的变化成分。Luminex检测38种血浆细胞因子和趋化因子的水平。体外构建富含前表面活性蛋白B（pro-SFTPB）的HDL，以证实其对THP1来源巨噬细胞M1极化的影响。

结果

从发现队列中鉴定出的102种HDL变化蛋白中验证了18种蛋白，包括HDL颗粒成分，如载脂蛋白、称为血清淀粉样蛋白A（SAA）的促炎物质以及如对氧磷酶（PON）的抗氧化蛋白。在这些蛋白中，只有HDL中pro-SFTPB的增加与ARDS患者的不良预后显著相关。值得注意的是，HDL-pro-SFTPB水平与血浆促炎细胞因子和趋化因子水平相关。pro-SFTPB与其他HDL成分的相关性分析表明，它分别与SAA2和PON3呈正相关和负相关。此外，体外研究证实富含pro-SFTPB的HDL显著促进单核细胞来源巨噬细胞的M1极化。