TY - JOUR T1 - Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice JF - European Respiratory Journal JO - Eur Respir J SP - 1451 LP - 1460 DO - 10.1183/09031936.00216914 VL - 46 IS - 5 AU - Mathieu C. Morissette AU - Pamela Shen AU - Danya Thayaparan AU - Martin R. Stämpfli Y1 - 2015/11/01 UR - http://erj.ersjournals.com/content/46/5/1451.abstract N2 - Overwhelming evidence links inflammation to the pathogenesis of smoking-related pulmonary diseases, especially chronic obstructive pulmonary disease (COPD). Despite an increased understanding of the disease pathogenesis, mechanisms initiating smoking-induced inflammatory processes remain incompletely understood.To investigate the mechanisms that initiate and propagate smoke-induced inflammation, we used a well-characterised mouse model of cigarette smoke exposure, mice deficient for interleukin (IL)-1α, IL-1β and Toll-like receptor 4, and antibodies blocking granulocyte-macrophage colony-stimulating factor (GM-CSF). Studies were also pursued using intranasal delivery of human oxidised low-density lipoprotein (hOxLDL), a source of oxidised lipids, to investigate the inflammatory processes associated with impaired lipid homeostasis.We found that cigarette smoke exposure rapidly led to lipid accumulation in pulmonary macrophages, a defining feature of foam cells, which in turn released high levels of IL-1α. In smoke-exposed IL-1α-deficient mice, phospholipids accumulated in the bronchoalveolar lavage, a phenomenon also observed when blocking GM-CSF. Intranasal administration of hOxLDL led to lipid accumulation in macrophages and initiated an inflammatory process that mirrored the characteristics of cigarette smoke-induced inflammation.These findings identify a link between lipid accumulation in macrophages, inflammation and damaged surfactant, suggesting that the response to damaged pulmonary surfactant is a central mechanism that drives cigarette smoke-induced inflammation. Further investigations are required to explore the role of distorted lipid homeostasis in the pathogenesis of COPD.Lipid accumulation in pulmonary macrophages drives cigarette smoke-induced lung inflammation http://ow.ly/M0L0U ER -