Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/110503
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dc.contributor.authorTran, H.-
dc.contributor.authorJersmann, H.-
dc.contributor.authorTruong, T.-
dc.contributor.authorHamon, R.-
dc.contributor.authorRoscioli, E.-
dc.contributor.authorWeen, M.-
dc.contributor.authorPitman, M.-
dc.contributor.authorPitson, S.-
dc.contributor.authorHodge, G.-
dc.contributor.authorReynolds, P.-
dc.contributor.authorHodge, S.-
dc.contributor.editorKou, Y.R.-
dc.date.issued2017-
dc.identifier.citationPLoS One, 2017; 12(11):e0179577-1-e0179577-14-
dc.identifier.issn1932-6203-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/2440/110503-
dc.description.abstractIntroduction: We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling. Methods: Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling. Results: Spns2 expression was significantly increased (p<0.05) in alveolar macrophages from current-smokers/COPD patients (n = 5) compared to healthy nonsmokers (n = 8) and non-smoker lung transplant patients (n = 4). Consistent with this finding, cigarette smoke induced a significant increase in Spns2 expression in both human alveolar and THP-1 macrophages. In contrast, a remarkable Spns2 down-regulation was noted in response to cigarette smoke in 16HBE14o- cell line (p<0.001 in 3 experiments), primary nasal epithelial cells (p<0.01 in 2 experiments), and in smoke-exposed mice (p<0.001, n = 6 animals per group). Spns2 was localized to cilia in primary bronchial epithelial cells. In both macrophage and epithelial cell types, Spns2 was also found localized to cytoplasm and the nucleus, in line with a predicted bipartile Nuclear Localization Signal at the position aa282 of the human Spns2 sequence. In smoke-exposed mice, alveolar macrophage phagocytic function positively correlated with Spns2 protein expression in bronchial epithelial cells. Conclusion: Our data suggest that the epithelium may be the major source for extracellular S1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via Spns2-mediated S1P signaling in COPD and in response to cigarette smoke exposure.-
dc.description.statementofresponsibilityHai B. Tran, Hubertus Jersmann, Tung Thanh Truong, Rhys Hamon, Eugene Roscioli, Miranda Ween, Melissa R. Pitman, Stuart M. Pitson, Greg Hodge, Paul N. Reynolds, Sandra Hodge-
dc.language.isoen-
dc.publisherPLOS - Public Library of Science-
dc.rights© 2017 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.-
dc.source.urihttp://dx.doi.org/10.1371/journal.pone.0179577-
dc.subjectEpithelial Cells-
dc.titleDisrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD-
dc.typeJournal article-
dc.identifier.doi10.1371/journal.pone.0179577-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1044414-
pubs.publication-statusPublished-
dc.identifier.orcidTran, H. [0000-0002-9463-4033]-
dc.identifier.orcidJersmann, H. [0000-0003-1763-2736]-
dc.identifier.orcidHamon, R. [0000-0002-5474-8490]-
dc.identifier.orcidRoscioli, E. [0000-0002-3201-3899]-
dc.identifier.orcidWeen, M. [0000-0002-0600-4585]-
dc.identifier.orcidPitman, M. [0000-0002-9587-3837]-
dc.identifier.orcidPitson, S. [0000-0002-9527-2740]-
dc.identifier.orcidReynolds, P. [0000-0002-2273-1774]-
dc.identifier.orcidHodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]-
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