Dendritic Cells in the Pathogenesis of Cigarette Smoke-Induced Emphysema in Mice

Objectives: The recruitment and activation of inflammatory cells into the respiratory system is considered a crucial feature in the pathophysiology of chronic obstructive pulmonary disease (COPD). Because dendritic cells (DCs) have a pivotal role in the onset and regulation of immune responses, we investigated the effect of modulating DC subsets on airway inflammation in an animal model of cigarette smoke (CS) induced lung emphysema.Materials Methods: CS-exposed mice (3 month nose only exposure) were treated with fms-like tyrosine kinase 3 ligand (Flt3L) and 120g8 antibody to increase total DC numbers and deplete plasmacytoid DCs (pDCs), respectively. 24 hours after the last exposure to smoke, airway responsiveness was assessed and mice were sacrificed. The bronchoalveolar lavage fluid (BALF) were collected for cell and cytokine profilestudies andthe Lungs of animals were subjected to morphometric analysis.Results and conclusion: Flt3L treatment decreased the number of inflammatory cells and increased the level of Fibroblast growth factor and vascular endothelial growth factor in the BALF of the smoke-exposed mice. Furthermore, the increase in the mean linear intercept (Lm) following Flt3L treatment was decreased by pDC depletion which might suggest a role for pDC as a promoter for development of lung emphysema and lung function reduction through smoking. This study suggest thatm DC are likely to be responsible for growth factors production in lung and modulation of DC subsets by pharmacological agents might be critical in the pathogenesis of the lung emphysema induced by cigarette smoke.