PMID- 32082309
OWN - NLM
STAT- MEDLINE
DCOM- 20210219
LR  - 20210219
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing 
      Polarization of M2 Subtype Macrophages.
PG  - 11
LID - 10.3389/fimmu.2020.00011 [doi]
LID - 11
AB  - Calreticulin (CALR) has anti-tumor effects by increasing dendritic cell 
      maturation and tumor antigen presentation. However, whether CALR affects 
      macrophages and modulates progression of acute respiratory distress 
      syndrome/acute lung injury (ARDS/ALI) remains unknown. In this study, we 
      discovered that CALR protein was highly expressed in the mice with LPS-induced 
      ALI and CALR expression level was positively correlated to the severity of ALI. 
      Commercial anti-CALR antibody (aCALR) can neutralize recombinant CALR (rCALR) and 
      suppress the expression of TNF-alpha and IL-6 in the rCALR-treated macrophages. 
      Blocking CALR activity by intraperitoneal (i.p.) administration of aCALR 
      significantly suppressed ALI, accompanied with lower total cell counts, 
      neutrophil and T cell infiltration in bronchoalveolar lavage (BAL) and lung 
      tissues. The expression of CXCL15, IL-6, IL-1beta, TNF-alpha, and CALR were 
      significantly reduced, in association with more polarization of Siglec F+CD206+M2 
      subtype macrophages in the aCALR-treated mice. Pre-depletion of circulating 
      monocytes did not abolish the aCALR-mediated suppression of ALI. Further analysis 
      in bone marrow-derived macrophages (BMDMs) showed that aCALR suppressed the 
      expression of CD80, IL-6, IL-1beta, IL-18, NLRP3, and p-p38 MAPK; but enhanced 
      the expression of CD206 and IL-10. In addition, we observed more expression and 
      phosphorylation of STAT6 in the aCALR-treated BMDM. Lack of STAT6 resulted in 
      comparable and slightly higher expression of CALR, TNF-alpha and IL-6 in the 
      aCALR-treated STAT6-/- BMDMs than the untreated cells. Therefore, we conclude 
      that CALR is a novel biomarker in the evaluation of ALI. Blocking CALR activity 
      by aCALR effectively suppressed ALI independent of circulating monocytes. Siglec 
      F+CD206+M2 subtype macrophages and p38 MAPK/STAT6 signaling pathway played 
      important role in the immune regulation of aCALR. Blocking CALR activity is a 
      promising therapeutic approach in the treatment of ARDS/ALI.
CI  - Copyright (c) 2020 Jiang, Chen, Hu, Qiu and Zhu.
FAU - Jiang, Zhilong
AU  - Jiang Z
AD  - Department of Pulmonary Medicine, Fudan University Zhongshan Hospital, Shanghai, 
      China.
FAU - Chen, Zhihong
AU  - Chen Z
AD  - Department of Pulmonary Medicine, Fudan University Zhongshan Hospital, Shanghai, 
      China.
FAU - Hu, Lu
AU  - Hu L
AD  - Department of Pulmonary Medicine, Fudan University Zhongshan Hospital, Shanghai, 
      China.
FAU - Qiu, Lin
AU  - Qiu L
AD  - Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, 
      Shanghai, China.
FAU - Zhu, Lei
AU  - Zhu L
AD  - Department of Pulmonary Medicine, Fudan University Zhongshan Hospital, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200130
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies)
RN  - 0 (Calreticulin)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Stat6 protein, mouse)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acute Lung Injury/blood/chemically induced/*drug therapy
MH  - Animals
MH  - Antibodies/*administration & dosage/*immunology
MH  - Calreticulin/*antagonists & inhibitors/blood/*immunology
MH  - Cell Polarity/*drug effects/immunology
MH  - Cytokines/blood
MH  - Disease Models, Animal
MH  - Injections, Intraperitoneal
MH  - Lipopolysaccharides/adverse effects
MH  - Macrophages/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Recombinant Proteins/immunology/metabolism
MH  - Respiratory Distress Syndrome/drug therapy
MH  - STAT6 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC7002388
OTO - NOTNLM
OT  - acute lung injury (ALI)
OT  - anti-calreticulin antibody (aCALR)
OT  - calreticulin (CALR)
OT  - cytokines
OT  - macrophages
EDAT- 2020/02/23 06:00
MHDA- 2021/02/20 06:00
PMCR- 2020/01/01
CRDT- 2020/02/22 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2020/01/06 00:00 [accepted]
PHST- 2020/02/22 06:00 [entrez]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2021/02/20 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.00011 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jan 30;11:11. doi: 10.3389/fimmu.2020.00011. eCollection 
      2020.