Extracellular HMGB1 Impairs Macrophage-Mediated Efferocytosis by Suppressing the Rab43-Controlled Cell Surface Transport of CD91.
Extracellular HMGB1 Impairs Macrophage-Mediated Efferocytosis by Suppressing the Rab43-Controlled Cell Surface Transport of CD91.
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细胞外 HMGB1 通过抑制 Rab43 控制的 CD91 细胞表面转运来损害巨噬细胞介导的胞吞作用
DOI：
10.3389/fimmu.2022.767630
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发表时间：
2022
影响因子：
7.3
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Wang Y;Zhang W;Xu Y;Wu D;Gao Z;Zhou J;Qian H;He B;Wang G
高迁移率族蛋白 1 (HMGB1) 蛋白可通过抑制巨噬细胞介导的凋亡细胞 (AC) 清除来损害吞噬细胞功能，从而延迟肺部炎症消退并导致急性肺损伤 (ALI) 和急性呼吸窘迫综合征 (ARDS) 的进展。然而，HMGB1 介导的胞吞作用抑制的确切机制仍不清楚。本研究的目的是确定 HMGB1 对巨噬细胞介导的胞吞作用的影响。我们发现 HMGB1 可以阻止骨髓源性巨噬细胞 (BMDM) 的胞吞作用，并抑制 Ras 相关 GTP 结合蛋白 43 (Rab43)（Ras 相关结合 (Rab) 家族成员）的表达。 Rab43 表达的下调导致 BMDM 对凋亡胸腺细胞的清除受损。对 HMGB1 处理和 Rab43 缺陷的 BMDM 的后续分析揭示了吞噬细胞识别受体分化簇 91 (CD91) 从细胞质到细胞表面的转运受到抑制。值得注意的是，Rab43 直接与 CD91 相互作用以介导其细胞间运输。此外，Rab43敲除延迟了ALI小鼠的炎症消退并加剧了肺组织损伤。因此，我们的结果提供了证据，证明 HMGB1 通过抑制 Rab43 调节的 CD91 顺行转运来损害巨噬细胞介导的胞吞作用并延迟炎症消退，这表明恢复 Rab43 水平是减轻人类 ALI 和 ARDS 的有前途的策略。
High-mobility group box 1 (HMGB1) protein can impair phagocyte function by suppressing the macrophage-mediated clearance of apoptotic cells (ACs), thereby delaying inflammation resolution in the lungs and allowing the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the precise mechanism underlying this HMGB1-mediated inhibition of efferocytosis remains unknown. The aim of this study was to determine the effect of HMGB1 on macrophage-mediated efferocytosis. We discovered that HMGB1 prevented efferocytosis by bone marrow-derived macrophages (BMDMs) and suppressed the expression of Ras-related GTP-binding protein 43 (Rab43), a member of the Ras-associated binding (Rab) family. The downregulation of Rab43 expression resulted in impaired clearance of apoptotic thymocytes by BMDMs. Subsequent analysis of HMGB1-treated and Rab43-deficient BMDMs revealed the inhibited transport of cluster of differentiation 91 (CD91), a phagocyte recognition receptor, from the cytoplasm to the cell surface. Notably, Rab43 directly interacted with CD91 to mediate its intercellular trafficking. Furthermore, Rab43 knockout delayed the inflammation resolution and aggravated the lung tissue damage in mice with ALI. Therefore, our results provide evidence that HMGB1 impairs macrophage-mediated efferocytosis and delays inflammation resolution by suppressing the Rab43-regulated anterograde transport of CD91, suggesting that the restoration of Rab43 levels is a promising strategy for attenuating ALI and ARDS in humans.
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影响因子：
3.7
作者：
Egami Y;Araki N
通讯作者：
Araki N
影响因子：
8.8
作者：
Li C;Wei Z;Fan Y;Huang W;Su Y;Li H;Dong Z;Fukuda M;Khater M;Wu G
通讯作者：
Wu G
DOI：
10.4049/jimmunol.1601495
发表时间：
2017-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jiang C;Liu Z;Hu R;Bo L;Minshall RD;Malik AB;Hu G
通讯作者：
Hu G
影响因子：
10.6
作者：
Kang, Rui;Chen, Ruochan;Zhang, Qiuhong;Hou, Wen;Wu, Sha;Cao, Lizhi;Huang, Jin;Yu, Yan;Fan, Xue-gong;Yan, Zhengwen;Sun, Xiaofang;Wang, Haichao;Wang, Qingde;Tsung, Allan;Billiar, Timothy R.;Zeh, Herbert J., III;Lotze, Michael T.;Tang, Daolin
通讯作者：
Tang, Daolin
影响因子：
5.3
作者：
Grailer JJ;Haggadone MD;Sarma JV;Zetoune FS;Ward PA
通讯作者：
Ward PA