title: The role of dendritic cells in the pathogenesis of cigarette smoke-induced emphysema in mice.
abstract: Chronic Obstructive Pulmonary Disease (COPD) is an important lung and airway disease which affects the lives of around 200 million people worldwide. The pathological hallmark of COPD is emphysema and bronchiolitis and is based on the inflammatory response of the innate and adaptive immune system to the inhalation of toxic particles and gases. The inflamed airways of COPD patients contain several inflammatory cells including neutrophils, macrophages, T lymphocytes, and dendritic cells (DC). The potential role of DCs as mediators of inflammation in the airways of smokers and COPD patients is poorly understood. The current study investigated the role of DC subsets in an animal model of cigarette smoke-induced lung emphysema through the expansion or depletion of DC subsets. Expansion of both myeloid DC (mDC) and plasmacytoid DC (pDC) by Flt3L treatment induced a decline in macrophage numbers and increased the levels of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) in the bronchoalveolar lavage (BAL) fluid of smoke-exposed animals. The increase in the mean linear intercept (Lm) following Flt3L treatment was decreased by pDC depletion. In conclusion, pharmacological modulation of DC subsets may have an effect on the development of airway responses and emphysema as indicated by the decline in macrophage numbers and the increase in FGF and VEGF levels in the bronchoalveolar lavage fluid. Moreover, the depletion of pDCs decreased the Lm which might suggest a role for pDC in the pathogenesis of lung emphysema.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Masoumeh E
authors.initials: ME
authors.lastname: Givi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Peck
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mortaz
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004646:Emphysema / Q000209:etiology* / Q000276:immunology*; D048788:Growth and Development / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000906:Antibodies; D008565:Membrane Proteins; C084881:flt3 ligand protein
keywords: Cigarette smoke; Dendritic cell; Emphysema