PMID- 34484184
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Lower Oligomeric Form of Surfactant Protein D in Murine Acute Lung Injury Induces 
      M1 Subtype Macrophages Through Calreticulin/p38 MAPK Signaling Pathway.
PG  - 687506
LID - 10.3389/fimmu.2021.687506 [doi]
LID - 687506
AB  - Surfactant protein D (SP-D) plays an important role in innate and adaptive immune 
      responses. In this study, we found that the expression of total and 
      de-oligomerized SP-D was significantly elevated in mice with lipopolysaccharide 
      (LPS)-induced acute lung injury (ALI). To investigate the role of the lower 
      oligomeric form of SP-D in the pathogenesis of ALI, we treated bone 
      marrow-derived macrophages (BMDMs) with ALI-derived bronchoalveolar lavage (BAL) 
      and found that SP-D in ALI BAL predominantly bound to calreticulin (CALR) on 
      macrophages, subsequently increasing the phosphorylation of p38 mitogen-activated 
      protein kinase (MAPK) and expression of interleukin (IL)-6, tumor necrosis factor 
      (TNF)-alpha, IL-10, and CD80. However, anti-SP-D (aSP-D) and anti-calreticulin 
      (aCALR) pretreatment reversed the SP-D binding and activation of macrophages 
      induced by ALI BAL or de-oligomerized recombinant murine SP-D (rSP-D). Lack of 
      signal transducer and activator of transcription (STAT)6 in STAT6-/- macrophages 
      resulted in resistance to suppression by aCALR. Further studies in an ALI mouse 
      model showed that blockade of pulmonary SP-D by intratracheal (i.t.), but not 
      intraperitoneal (i.p.), administration of aSP-D attenuated the severity of ALI, 
      accompanied by lower neutrophil infiltrates and expression of IL-1beta and IL-6. 
      Furthermore, i.t. administration of de-oligomerized rSP-D exacerbated the 
      severity of ALI in association with more pro-inflammatory CD45+Siglec-F(-) M1 
      subtype macrophages and production of IL-6, TNF-alpha, IL-1beta, and IL-18. The 
      results indicated that SP-D in the lungs of murine ALI was de-oligomerized and 
      participated in the pathogenesis of ALI by predominantly binding to CALR on 
      macrophages and subsequently activating the pro-inflammatory downstream signaling 
      pathway. Targeting de-oligomerized SP-D is a promising therapeutic strategy for 
      the treatment of ALI and acute respiratory distress syndrome (ARDS).
CI  - Copyright (c) 2021 Li, Pan, Zhang and Jiang.
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.
AD  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Pan, Linyue
AU  - Pan L
AD  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Zhang, Xiaoju
AU  - Zhang X
AD  - Department of Pulmonary and Critical Care Medicine, Henan Provincial People's 
      Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 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 - 20210816
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies)
RN  - 0 (Calb2 protein, mouse)
RN  - 0 (Calbindin 2)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pulmonary Surfactant-Associated Protein D)
RN  - 0 (lipopolysaccharide, E coli O55-B5)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acute Lung Injury/chemically induced/drug therapy/*enzymology/immunology
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Calbindin 2/antagonists & inhibitors/*metabolism
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides
MH  - Lung/drug effects/*enzymology/immunology/pathology
MH  - *Macrophage Activation/drug effects
MH  - Macrophages/drug effects/*enzymology/immunology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NIH 3T3 Cells
MH  - Neutrophil Infiltration
MH  - Phenotype
MH  - Phosphorylation
MH  - Pulmonary Surfactant-Associated Protein D/antagonists & inhibitors/*metabolism
MH  - RAW 264.7 Cells
MH  - Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC8415422
OTO - NOTNLM
OT  - acute lung injury
OT  - calreticulin
OT  - macrophages
OT  - signal regulatory protein-alpha
OT  - surfactant protein D
COIS- The funders had no role in the study design, data collection and analysis, 
      decision to publish, or preparation of the manuscript. 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- 2021/09/07 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/01/01
CRDT- 2021/09/06 05:55
PHST- 2021/03/29 00:00 [received]
PHST- 2021/07/27 00:00 [accepted]
PHST- 2021/09/06 05:55 [entrez]
PHST- 2021/09/07 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.687506 [doi]
PST - epublish
SO  - Front Immunol. 2021 Aug 16;12:687506. doi: 10.3389/fimmu.2021.687506. eCollection 
      2021.