PMID- 23637858
OWN - NLM
STAT- MEDLINE
DCOM- 20131111
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 4
DP  - 2013
TI  - Defective lung macrophage function in lung cancer +/- chronic obstructive pulmonary 
      disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
PG  - e61573
LID - 10.1371/journal.pone.0061573 [doi]
LID - e61573
AB  - 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.
FAU - Dehle, Francis C
AU  - Dehle FC
AD  - Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia.
FAU - Mukaro, Violet R
AU  - Mukaro VR
FAU - Jurisevic, Craig
AU  - Jurisevic C
FAU - Moffat, David
AU  - Moffat D
FAU - Ahern, Jessica
AU  - Ahern J
FAU - Hodge, Greg
AU  - Hodge G
FAU - Jersmann, Hubertus
AU  - Jersmann H
FAU - Reynolds, Paul N
AU  - Reynolds PN
FAU - Hodge, Sandra
AU  - Hodge S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130426
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Bronchoalveolar Lavage Fluid
MH  - Cell Line, Tumor
MH  - Cyclooxygenase 2/metabolism
MH  - Demography
MH  - Dinoprostone/*biosynthesis
MH  - Female
MH  - Humans
MH  - Lung/*metabolism/*pathology
MH  - Lung Neoplasms/*complications/pathology
MH  - Macrophages, Alveolar/*pathology
MH  - Male
MH  - Middle Aged
MH  - Phagocytosis
MH  - Pulmonary Disease, Chronic Obstructive/*complications/pathology
MH  - Pulmonary Emphysema/*complications/pathology
MH  - Subcellular Fractions/metabolism
PMC - PMC3637201
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/03 06:00
MHDA- 2013/11/12 06:00
PMCR- 2013/04/26
CRDT- 2013/05/03 06:00
PHST- 2012/11/29 00:00 [received]
PHST- 2013/03/11 00:00 [accepted]
PHST- 2013/05/03 06:00 [entrez]
PHST- 2013/05/03 06:00 [pubmed]
PHST- 2013/11/12 06:00 [medline]
PHST- 2013/04/26 00:00 [pmc-release]
AID - PONE-D-12-37940 [pii]
AID - 10.1371/journal.pone.0061573 [doi]
PST - epublish
SO  - PLoS One. 2013 Apr 26;8(4):e61573. doi: 10.1371/journal.pone.0061573. Print 2013.