Efferocytosis impairs pulmonary macrophage and lung antibacterial function via PGE2/EP2 signaling.

The Journal of Experimental Medicine
Alexandra I MedeirosMarc Peters-Golden

Abstract

The ingestion of apoptotic cells (ACs; termed "efferocytosis") by phagocytes has been shown to trigger the release of molecules such as transforming growth factor beta, interleukin-10 (IL-10), nitric oxide, and prostaglandin E(2) (PGE(2)). Although the antiinflammatory actions of these mediators may contribute to the restoration of homeostasis after tissue injury, their potential impact on antibacterial defense is unknown. The lung is highly susceptible to diverse forms of injury, and secondary bacterial infections after injury are of enormous clinical importance. We show that ACs suppress in vitro phagocytosis and bacterial killing by alveolar macrophages and that this is mediated by a cyclooxygenase-PGE(2)-E prostanoid receptor 2 (EP2)-adenylyl cyclase-cyclic AMP pathway. Moreover, intrapulmonary administration of ACs demonstrated that PGE(2) generated during efferocytosis and acting via EP2 accounts for subsequent impairment of lung recruitment of polymorphonuclear leukocytes and clearance of Streptococcus pneumoniae, as well as enhanced generation of IL-10 in vivo. These results suggest that in addition to their beneficial homeostatic influence, antiinflammatory programs activated by efferocytosis in the lung have the undes...Continue Reading

References

Sep 3, 1985·Journal of Immunological Methods·R Peck
Aug 1, 1995·American Journal of Respiratory and Critical Care Medicine·K R SutherlandL D Hudson
Dec 6, 1997·Nature·R E VollI Girkontaite
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·H HizakiA Ichikawa
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·B HuJ L Curtis
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·B B MooreG B Toews
Dec 6, 2000·The Journal of Clinical Investigation·Y KasaharaN F Voelkel
Mar 13, 2001·Annual Review of Immunology·J V Ravetch, S Bolland
Jan 10, 2002·The Journal of Clinical Investigation·Mai-Lan N HuynhPeter M Henson
Mar 6, 2002·The Journal of Clinical Investigation·R William VandivierPeter M Henson
Dec 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Uwe KoedelCarsten J Kirschning
Sep 17, 2003·Critical Care : the Official Journal of the Critical Care Forum·Gustavo Matute-Bello, Thomas R Martin
Oct 7, 2003·American Journal of Respiratory Cell and Molecular Biology·Bin HuJeffrey L Curtis
Feb 24, 2004·Infection and Immunity·Alexandra I MedeirosLúcia H Faccioli
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·David M AronoffMarc Peters-Golden
Jul 21, 2004·The Journal of Experimental Medicine·Mohamed ArredouaniLester Kobzik
Jan 7, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·David M AronoffMarc Peters-Golden
Jan 13, 2006·PLoS Medicine·Joseph P Mizgerd
Jan 24, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·David M AronoffMarc Peters-Golden
Mar 3, 2007·European Journal of Immunology·Ruxana T SadikotJohn W Christman
May 8, 2007·Lancet·Arthur P Wheeler, Gordon R Bernard
Jun 23, 2007·American Journal of Respiratory Cell and Molecular Biology·Carlos H SerezaniMarc Peters-Golden
Aug 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guangwen RenYufang Shi
Sep 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christopher D SibleyMichael G Surette

❮ Previous
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Citations

Jun 26, 2013·Trends in Pharmacological Sciences·Jianxiong Jiang, Ray Dingledine
Aug 3, 2010·Nature Reviews. Microbiology·Samuel M BeharHeinz G Remold
Feb 8, 2011·The Journal of Biological Chemistry·S Courtney FraschDonna L Bratton
Jan 8, 2013·The Journal of Biological Chemistry·S Courtney FraschDonna L Bratton
May 1, 2013·The Journal of Experimental Medicine·Jennifer H MadenspacherMichael B Fessler
Oct 4, 2012·The Journal of Infectious Diseases·Deepak Kaushal
Aug 10, 2010·Current Opinion in Rheumatology·Robert J Homer, Erica L Herzog
Oct 2, 2012·Mediators of Inflammation·Alexandra MedeirosC Henrique Serezani
Apr 17, 2010·American Journal of Respiratory and Critical Care Medicine·David W DraperMichael B Fessler
Aug 10, 2013·Investigative Ophthalmology & Visual Science·Shayma JawadRobert B Nussenblatt
May 11, 2011·Journal of Neuroinflammation·Lalida RojanathammaneeColin K Combs
Mar 31, 2009·Future Microbiology·Tracy HussellJohn Goulding
Jan 11, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sun Wook ChoLaurie K McCauley
Dec 5, 2012·Mediators of Inflammation·Cassiano Felippe Gonçalves-de-AlbuquerqueMauro Velho de Castro Faria
Mar 10, 2016·Seminars in Immunopathology·Aleksander M Grabiec, Tracy Hussell
Mar 30, 2016·Nature Reviews. Drug Discovery·James N Fullerton, Derek W Gilroy
Apr 5, 2015·Apoptosis : an International Journal on Programmed Cell Death·Minqiang LiuJianping Xie
Jul 1, 2016·Antioxidants & Redox Signaling·Joslyn M AlbrightElizabeth J Kovacs
Mar 25, 2014·Immunity·Christopher D BuckleyCharles N Serhan
Jun 5, 2013·Chest·Alexandra L McCubbrey, Jeffrey L Curtis
Oct 23, 2009·British Journal of Pharmacology·Terence Peters, Peter J Henry
Apr 15, 2014·Nature Medicine·Alastair J O'BrienDerek W Gilroy
Feb 6, 2018·Annual Review of Immunology·Shigekazu Nagata
Oct 11, 2017·Expert Review of Clinical Immunology·Maryam ImanJafar Salimian
Dec 21, 2012·Journal of Cellular Physiology·Sonia EliginiSusanna Colli

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Methods Mentioned

BETA
flow cytometry
bronchoalveolar lavage
Assay
ELISAs
lavage
ELISA
light microscopy

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