PMID- 35392093
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20220531
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Extracellular HMGB1 Impairs Macrophage-Mediated Efferocytosis by Suppressing the 
      Rab43-Controlled Cell Surface Transport of CD91.
PG  - 767630
LID - 10.3389/fimmu.2022.767630 [doi]
LID - 767630
AB  - 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.
CI  - Copyright (c) 2022 Wang, Zhang, Xu, Wu, Gao, Zhou, Qian, He and Wang.
FAU - Wang, Yao
AU  - Wang Y
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhang, Wen
AU  - Zhang W
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
FAU - Xu, Yu
AU  - Xu Y
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
FAU - Wu, Di
AU  - Wu D
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
FAU - Gao, Zhan
AU  - Gao Z
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhou, Jianchun
AU  - Zhou J
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Chongqing Medical University, Chongqing, China.
FAU - Qian, Hang
AU  - Qian H
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
FAU - He, Binfeng
AU  - He B
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
AD  - Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
FAU - Wang, Guansong
AU  - Wang G
AD  - Institute of Respiratory Diseases, Department of Pulmonary and Critical Care 
      Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20220322
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, mouse)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (Lrp1 protein, mouse)
RN  - EC 3.6.5.2 (Rab44 protein, mouse)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - *Acute Lung Injury/metabolism
MH  - Animals
MH  - *HMGB1 Protein/metabolism
MH  - Inflammation/metabolism
MH  - *Low Density Lipoprotein Receptor-Related Protein-1/metabolism
MH  - *Macrophages/metabolism
MH  - Mice
MH  - Phagocytosis
MH  - *Respiratory Distress Syndrome
MH  - *rab GTP-Binding Proteins/metabolism
PMC - PMC8980266
OTO - NOTNLM
OT  - ARDS
OT  - CD91
OT  - HMGB1
OT  - Rab43
OT  - macrophage
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/09 06:00
MHDA- 2022/04/12 06:00
PMCR- 2022/01/01
CRDT- 2022/04/08 05:15
PHST- 2021/08/31 00:00 [received]
PHST- 2022/02/22 00:00 [accepted]
PHST- 2022/04/08 05:15 [entrez]
PHST- 2022/04/09 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.767630 [doi]
PST - epublish
SO  - Front Immunol. 2022 Mar 22;13:767630. doi: 10.3389/fimmu.2022.767630. eCollection 
      2022.