Danya Thayaparan1, Pamela Shen1, Martin R Stämpfli2,3, Mathieu C Morissette4,5. 1. Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada. 2. Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada. 3. Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, ON, Canada. 4. Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725, Chemin Ste-Foy, G1V 4G5, Quebec City, PQ, Canada. mathieu.morissette@criucpq.ulaval.ca. 5. Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, PQ, Canada. mathieu.morissette@criucpq.ulaval.ca.
Abstract
BACKGROUND: Chronic cigarette smoke exposure is known to activate the adaptive immune system; however, the functional role of these processes is currently unknown. Given the role of oxidized lipids in driving innate inflammatory responses to cigarette smoke, we investigated whether an adaptive immune response against damaged lipids was induced following chronic cigarette smoke exposure. METHODS AND RESULTS: Using a well-established mouse model, we showed that cigarette smoke exposure led to a progressive increase in pulmonary antibodies against oxidized low-density lipoprotein (OxLDL). Functionally, we found that intranasal delivery of an antibody against oxidized phosphatidylcholine (anti-OxPC; clone E06) increased lipid and particle uptake by pulmonary macrophages without exacerbating cigarette smoke-induced neutrophilia. We also found that anti-OxPC treatment increased particle uptake following smoking cessation. Finally, the frequency of pulmonary macrophages with internalized particles was increased after prolonged smoke exposure, at which time lung anti-OxPC responses were highest. CONCLUSIONS: Altogether, this is the first report to demonstrate a non-pathogenic, and possibly protective, function of a newly identified autoantibody induced by chronic cigarette smoke exposure.
BACKGROUND: Chronic cigarette smoke exposure is known to activate the adaptive immune system; however, the functional role of these processes is currently unknown. Given the role of oxidized lipids in driving innate inflammatory responses to cigarette smoke, we investigated whether an adaptive immune response against damaged lipids was induced following chronic cigarette smoke exposure. METHODS AND RESULTS: Using a well-established mouse model, we showed that cigarette smoke exposure led to a progressive increase in pulmonary antibodies against oxidized low-density lipoprotein (OxLDL). Functionally, we found that intranasal delivery of an antibody against oxidized phosphatidylcholine (anti-OxPC; clone E06) increased lipid and particle uptake by pulmonary macrophages without exacerbating cigarette smoke-induced neutrophilia. We also found that anti-OxPC treatment increased particle uptake following smoking cessation. Finally, the frequency of pulmonary macrophages with internalized particles was increased after prolonged smoke exposure, at which time lung anti-OxPC responses were highest. CONCLUSIONS: Altogether, this is the first report to demonstrate a non-pathogenic, and possibly protective, function of a newly identified autoantibody induced by chronic cigarette smoke exposure.
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