PMID- 35634325
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Soluble SIRP-Alpha Promotes Murine Acute Lung Injury Through Suppressing 
      Macrophage Phagocytosis.
PG  - 865579
LID - 10.3389/fimmu.2022.865579 [doi]
LID - 865579
AB  - Soluble signal regulatory protein-alpha (SIRP-alpha) is elevated in 
      bronchoalveolar lavage (BAL) of mice with lipopolysaccharides (LPS)-induced acute 
      lung injury (ALI). To define the role of soluble SIRP-alpha in the pathogenesis 
      of ALI, we established murine ALI in wild-type (WT) and SIRP-alpha knock-out (KO) 
      mice by intratracheal administration of LPS. The results indicated that lack of 
      SIRP-alpha significantly reduced the pathogenesis of ALI, in association with 
      attenuated lung inflammation, infiltration of neutrophils and expression of 
      pro-inflammatory cytokines in mice. In addition, lack of SIRP-alpha reduced the 
      expression of pro-inflammatory cytokines in LPS-treated bone marrow-derived 
      macrophages (BMDMs) from KO mice, accompanied with improved macrophage 
      phagocytosis. Blockade of soluble SIRP-alpha activity in ALI BAL by 
      anti-SIRP-alpha antibody (aSIRP) effectively reduced the expression of TNF-alpha 
      and IL-6 mRNA transcripts and proteins, improved macrophage phagocytosis in 
      vitro. In addition, lack of SIRP-alpha reduced activation of Src homology 2 
      domain-containing protein tyrosine phosphatase 1 (SHP-1) and improved activation 
      of signal transducer and activator of transcription-3 (STAT3) and STAT6. 
      Suppression of SHP-1 activity by tyrosine phosphatase inhibitor 1 (TPI-1) 
      increased activation of STAT3 and STAT6, and improved macrophage phagocytosis, 
      that was effectively reversed by STAT3 and STAT6 inhibitors. Thereby, SIRP-alpha 
      suppressed macrophage phagocytosis through activation of SHP-1, subsequently 
      inhibiting downstream STAT3 and STAT6 signaling. Lack of SIRP-alpha attenuated 
      murine ALI possibly through increasing phagocytosis, and improving STAT3 and 
      STAT6 signaling in macrophages. SIRP-alpha would be promising biomarker and 
      molecular target in the treatment of murine ALI and patients with acute 
      respiratory distress syndrome (ARDS).
CI  - Copyright (c) 2022 Shen, Zhao, Pan, Li, Chen, Chen and Jiang.
FAU - Shen, Qinjun
AU  - Shen Q
AD  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Zhao, Li
AU  - Zhao L
AD  - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Pan, Linyue
AU  - Pan L
AD  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Li, Dandan
AU  - Li D
AD  - Department of Pulmonary and Critical Care Medicine, Henan Provincial People's 
      Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
FAU - Chen, Gang
AU  - Chen G
AD  - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Chen, Zhihong
AU  - Chen Z
AD  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Jiang, Zhilong
AU  - Jiang Z
AD  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220512
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - *Acute Lung Injury/pathology
MH  - Animals
MH  - Cytokines/metabolism
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages
MH  - Mice
MH  - Mice, Knockout
MH  - Phagocytosis
MH  - *Respiratory Distress Syndrome
PMC - PMC9133620
OTO - NOTNLM
OT  - SIRP-alpha
OT  - STAT3
OT  - STAT6
OT  - acute lung injury
OT  - macrophages
OT  - phagocytosis
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- 2022/06/01 06:00
MHDA- 2022/06/03 06:00
PMCR- 2022/01/01
CRDT- 2022/05/31 09:54
PHST- 2022/01/30 00:00 [received]
PHST- 2022/04/13 00:00 [accepted]
PHST- 2022/05/31 09:54 [entrez]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.865579 [doi]
PST - epublish
SO  - Front Immunol. 2022 May 12;13:865579. doi: 10.3389/fimmu.2022.865579. eCollection 
      2022.