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Investigation of Cigarette Smoke Oxidised Lipids on Macrophages
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A4760 - Investigation of Cigarette Smoke Oxidised Lipids on Macrophages
Author Block: M. Ween1, J. Whittall1, H. B. Tran2, S. J. Hodge3; 1Royal Adelaide Hospital, Adelaide, Australia, 2Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia, 3Medicine, University of Adelaide, Adelaide, Australia.
Rationale: Reduced apoptotic bronchial cell efferocytosis by alveolar macrophages and build-up of oxidised lipids has been described in COPD by us and others, but the flow on effects of increased lipids in the airways have been poorly investigated. We thus assessed whether cigarette smoke oxidised lipid could be isolated from bronchial epithelial cells, the oxidation status quantitated, and the effects of this lipid on monocyte derived macrophages (MDMs).
Methods: Cigarette smoke was bubbled through bronchial epithelial cells, before chloroform lipid extraction. Oxidation status was measured by assessing the levels of conjugated dienes detectable at 234nm. This lipid was quantitated by dry lipid film weight and used to treat MDMs. Surface markers and phagocytosis were assessed by flow cytometry.
Results: Airway epithelial cellular lipids were highly oxidised by cigarette smoke (~272% increase in conjugated dienes from controls). Treatment with CS-oxidised airway epithelial lipid increased lipid antigen presentation molecule CD1b in MDMs (87% vs 69%) and also significantly decreased NTHi phagocytosis (8.7% vs 16.5%) in a dose dependent manner. Co-treatment with the FDA approved sphingolipid modulator FTY720 abrogated the decreased phagocytosis suggesting the sphingolipid pathway is involved. We also show that alveolar macrophages from COPD patients and smokers have higher expression of CD1b than healthy controls (15.8% smoking COPD, 9.6% ex-smoker COPD, compared with 1.8% for control).
Conclusion: Oxidised lipids from uncleared apoptotic airway cells in COPD may be another reason for decreased phagocytosis in the airways in these patients and may also be presented by CD1b, potentially identifying an aberrant immune component of COPD. This provides a target which could be exploited by future treatment strategies manipulating the sphingolipid pathway.
Author Block: M. Ween1, J. Whittall1, H. B. Tran2, S. J. Hodge3; 1Royal Adelaide Hospital, Adelaide, Australia, 2Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia, 3Medicine, University of Adelaide, Adelaide, Australia.
Rationale: Reduced apoptotic bronchial cell efferocytosis by alveolar macrophages and build-up of oxidised lipids has been described in COPD by us and others, but the flow on effects of increased lipids in the airways have been poorly investigated. We thus assessed whether cigarette smoke oxidised lipid could be isolated from bronchial epithelial cells, the oxidation status quantitated, and the effects of this lipid on monocyte derived macrophages (MDMs).
Methods: Cigarette smoke was bubbled through bronchial epithelial cells, before chloroform lipid extraction. Oxidation status was measured by assessing the levels of conjugated dienes detectable at 234nm. This lipid was quantitated by dry lipid film weight and used to treat MDMs. Surface markers and phagocytosis were assessed by flow cytometry.
Results: Airway epithelial cellular lipids were highly oxidised by cigarette smoke (~272% increase in conjugated dienes from controls). Treatment with CS-oxidised airway epithelial lipid increased lipid antigen presentation molecule CD1b in MDMs (87% vs 69%) and also significantly decreased NTHi phagocytosis (8.7% vs 16.5%) in a dose dependent manner. Co-treatment with the FDA approved sphingolipid modulator FTY720 abrogated the decreased phagocytosis suggesting the sphingolipid pathway is involved. We also show that alveolar macrophages from COPD patients and smokers have higher expression of CD1b than healthy controls (15.8% smoking COPD, 9.6% ex-smoker COPD, compared with 1.8% for control).
Conclusion: Oxidised lipids from uncleared apoptotic airway cells in COPD may be another reason for decreased phagocytosis in the airways in these patients and may also be presented by CD1b, potentially identifying an aberrant immune component of COPD. This provides a target which could be exploited by future treatment strategies manipulating the sphingolipid pathway.
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