Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?

In chronic obstructive pulmonary disease (COPD/emphysema) we have shown a reduced ability of lung and alveolar (AM) macrophages to phagocytose apoptotic cells (defective 'efferocytosis'), associated with evidence of secondary cellular necrosis and a resultant inflammatory response in the a...

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Autores principales:	Francis C Dehle, Violet R Mukaro, Craig Jurisevic, David Moffat, Jessica Ahern, Greg Hodge, Hubertus Jersmann, Paul N Reynolds, Sandra Hodge
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/708bb7843b4d4f1fbecaa35318e64000
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spelling	oai:doaj.org-article:708bb7843b4d4f1fbecaa35318e640002021-11-18T07:47:47ZDefective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?1932-620310.1371/journal.pone.0061573https://doaj.org/article/708bb7843b4d4f1fbecaa35318e640002013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23637858/?tool=EBIhttps://doaj.org/toc/1932-6203In chronic obstructive pulmonary disease (COPD/emphysema) we have shown a reduced ability of lung and alveolar (AM) macrophages to phagocytose apoptotic cells (defective 'efferocytosis'), associated with evidence of secondary cellular necrosis and a resultant inflammatory response in the airway. It is unknown whether this defect is present in cancer (no COPD) and if so, whether this results from soluble mediators produced by cancer cells. We investigated efferocytosis in AM (26 controls, 15 healthy smokers, 37 COPD, 20 COPD+ non small cell lung cancer (NSCLC) and 8 patients with NSCLC without COPD) and tumor and tumor-free lung tissue macrophages (21 NSCLC with/13 without COPD). To investigate the effects of soluble mediators produced by lung cancer cells we then treated AM or U937 macrophages with cancer cell line supernatant and assessed their efferocytosis ability. We qualitatively identified Arachidonic Acid (AA) metabolites in cancer cells by LC-ESI-MSMS, and assessed the effects of COX inhibition (using indomethacin) on efferocytosis. Decreased efferocytosis was noted in all cancer/COPD groups in all compartments. Conditioned media from cancer cell cultures decreased the efferocytosis ability of both AM and U937 macrophages with the most pronounced effects occurring with supernatant from SCLC (an aggressive lung cancer type). AA metabolites identified in cancer cells included PGE2. The inhibitory effect of PGE2 on efferocytosis, and the involvement of the COX-2 pathway were shown. Efferocytosis is decreased in COPD/emphysema and lung cancer; the latter at least partially a result of inhibition by soluble mediators produced by cancer cells that include PGE2.Francis C DehleViolet R MukaroCraig JurisevicDavid MoffatJessica AhernGreg HodgeHubertus JersmannPaul N ReynoldsSandra HodgePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61573 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francis C Dehle Violet R Mukaro Craig Jurisevic David Moffat Jessica Ahern Greg Hodge Hubertus Jersmann Paul N Reynolds Sandra Hodge Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
description	In chronic obstructive pulmonary disease (COPD/emphysema) we have shown a reduced ability of lung and alveolar (AM) macrophages to phagocytose apoptotic cells (defective 'efferocytosis'), associated with evidence of secondary cellular necrosis and a resultant inflammatory response in the airway. It is unknown whether this defect is present in cancer (no COPD) and if so, whether this results from soluble mediators produced by cancer cells. We investigated efferocytosis in AM (26 controls, 15 healthy smokers, 37 COPD, 20 COPD+ non small cell lung cancer (NSCLC) and 8 patients with NSCLC without COPD) and tumor and tumor-free lung tissue macrophages (21 NSCLC with/13 without COPD). To investigate the effects of soluble mediators produced by lung cancer cells we then treated AM or U937 macrophages with cancer cell line supernatant and assessed their efferocytosis ability. We qualitatively identified Arachidonic Acid (AA) metabolites in cancer cells by LC-ESI-MSMS, and assessed the effects of COX inhibition (using indomethacin) on efferocytosis. Decreased efferocytosis was noted in all cancer/COPD groups in all compartments. Conditioned media from cancer cell cultures decreased the efferocytosis ability of both AM and U937 macrophages with the most pronounced effects occurring with supernatant from SCLC (an aggressive lung cancer type). AA metabolites identified in cancer cells included PGE2. The inhibitory effect of PGE2 on efferocytosis, and the involvement of the COX-2 pathway were shown. Efferocytosis is decreased in COPD/emphysema and lung cancer; the latter at least partially a result of inhibition by soluble mediators produced by cancer cells that include PGE2.
format	article
author	Francis C Dehle Violet R Mukaro Craig Jurisevic David Moffat Jessica Ahern Greg Hodge Hubertus Jersmann Paul N Reynolds Sandra Hodge
author_facet	Francis C Dehle Violet R Mukaro Craig Jurisevic David Moffat Jessica Ahern Greg Hodge Hubertus Jersmann Paul N Reynolds Sandra Hodge
author_sort	Francis C Dehle
title	Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
title_short	Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
title_full	Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
title_fullStr	Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
title_full_unstemmed	Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
title_sort	defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (copd/emphysema)-mediated by cancer cell production of pge2?
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/708bb7843b4d4f1fbecaa35318e64000
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Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?

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