title: Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
abstract: 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.
authors: Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia.
authors: Francis C
authors: FC
authors: Dehle
authors: Violet R
authors: VR
authors: Mukaro
authors: Craig
authors: C
authors: Jurisevic
authors: David
authors: D
authors: Moffat
authors: Jessica
authors: J
authors: Ahern
authors: Greg
authors: G
authors: Hodge
authors: Hubertus
authors: H
authors: Jersmann
authors: Paul N
authors: PN
authors: Reynolds
authors: Sandra
authors: S
authors: Hodge
mesh_terms: D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003710:Demography; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008175:Lung Neoplasms / Q000150:complications* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000150:complications* / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
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