STAT6 induces expression of Gas6 in macrophages to clear apoptotic neutrophils and resolve inflammation

Proceedings of the National Academy of Sciences of the United States of America
Saroj NepalAsrar B Malik

Abstract

Efferocytosis of apoptotic neutrophils (PMNs) by alveolar macrophages (AMФs) is vital for resolution of inflammation and tissue injury. Here, we investigated the role of AMФ polarization and expression of the efferocytic ligand Gas6 in restoring homeostasis. In the murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI), we observed augmented temporal generation of cytokines IL-4 and TSG6 in bronchoalveolar fluid (BALF). Interestingly, we also observed increased expression of antiinflammatory markers consistent with a phenotype shift in AMФs. In particular, AMФs expressed the efferocytic ligand Gas6. In vitro priming of bone marrow-derived macrophages (BMMФs) with IL-4 or TSG6 also induced MФ transition and expression of Gas6. TSG6- or IL-4-primed BMMФs induced efferocytosis of apoptotic PMNs compared with control BMMФs. Adoptive transfer of TSG6- or IL-4-primed BMMФs i.t. into LPS-challenged mice more rapidly and effectively cleared PMNs in lungs compared with control BMMФs. We demonstrated that expression of Gas6 during AMФ transition was due to activation of the transcription factor signal transducer and activator of transcription-6 (STAT6) downstream of IL-4 or TSG6 signaling. Adoptive transfer of Gas6-depl...Continue Reading

References

Oct 24, 1998·The Journal of Biological Chemistry·Y Ohmori, T A Hamilton
Apr 6, 2006·Trends in Immunology·Peter M Henson, David A Hume
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heather M SeitzGlenn K Matsushima
May 9, 2007·The Journal of Experimental Medicine·Ludovic ArnoldBénédicte Chazaud
Jul 16, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Gustavo Matute-BelloThomas R Martin
Jan 7, 2009·The Journal of Experimental Medicine·Alexandra I MedeirosMarc Peters-Golden
Jan 16, 2010·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Elizabeth R Johnson, Michael A Matthay
Dec 15, 2010·Nature Methods·Mark R LooneyMatthew F Krummel
Mar 29, 2011·Immunologic Research·Shreevrat Goenka, Mark H Kaplan
Oct 26, 2011·Nature Reviews. Immunology·Toby Lawrence, Gioacchino Natoli
Nov 9, 2011·Nature Medicine·Mia Phillipson, Paul Kubes
Mar 2, 2012·The Journal of Clinical Investigation·Antonio Sica, Alberto Mantovani
Jan 1, 2011·Frontiers in Immunology·Darlynn KornsDonna L Bratton
Jan 1, 2011·Frontiers in Immunology·Susanne HeroldJuergen Lohmeyer
Sep 18, 2012·Cell Host & Microbe·Constance J MartinSamuel M Behar
Feb 26, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jianbo WuGuochang Hu
May 4, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Derin TugalMukesh K Jain
Jun 5, 2013·Chest·Alexandra L McCubbrey, Jeffrey L Curtis
Mar 7, 2014·Blood·Jonathan H M van der MeerCornelis van 't Veer
Sep 10, 2014·Nature Immunology·Anna ZagórskaGreg Lemke
Aug 4, 2015·Current Protocols in Immunology·Muthulekha SwamydasMichail S Lionakis
Feb 21, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·F R D'AlessioN R Aggarwal
Mar 10, 2016·Seminars in Immunopathology·Aleksander M Grabiec, Tracy Hussell
Nov 5, 2016·Annual Review of Physiology·Peter J Murray
Dec 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Manish MittalAsrar B Malik
Jan 6, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chunling JiangGuochang Hu
Feb 9, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael R ElliottPatrick S Murphy
Jun 15, 2017·Annual Review of Cell and Developmental Biology·Peter M Henson
May 3, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiancai ZhongYoung-Joon Surh

❮ Previous
Next ❯

Citations

Jul 16, 2020·American Journal of Physiology. Cell Physiology·János G Filep, Amiram Ariel
Sep 13, 2020·Nature Communications·Tobias WeinbergerChristian Schulz
Aug 15, 2020·Frontiers in Cell and Developmental Biology·Stephen J BushDavid A Hume
Dec 17, 2019·Cell Metabolism·Bishuang CaiIra Tabas
Sep 10, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Amrit Kumar ShresthaBinoy Shivanna
Oct 31, 2020·Journal of Neuroinflammation·Juwen C DuBoisBridget Shafit-Zagardo
Jun 21, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Luciana P TavaresLirlândia P Sousa
May 17, 2021·Pharmacology & Therapeutics·Juliana P VagoFons A J van de Loo
Oct 28, 2021·Immunology·Apurwa Singhal, Sachin Kumar

❮ Previous
Next ❯

Methods Mentioned

BETA
bronchoalveolar lavage
ELISA
flow cytometry
nuclear translocation
immunoprecipitation
ChIP
ELISAs
density-gradient centrifugation
confocal microscopy
Assay

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Carcinogenesis
Reiko Akitake-KawanoTsutomu Chiba
Arteriosclerosis, Thrombosis, and Vascular Biology
Istvan BaloghB Dahlbäck
Critical Care : the Official Journal of the Critical Care Forum
Begoña Hurtado, P de Frutos
© 2021 Meta ULC. All rights reserved