Cigarette smoke (CS) is the main causative factor of chronic obstructive pulmonary disease (COPD). Current research supports the concept that airway inflammation is central to the development and progression of the disease. Studies have demonstrated that neutrophils are increased in COPD lungs and that neutrophilassociated products correlate with the development and severity of COPD. The peptide FMLP is an active component of CS. FMLP interacts on the neutrophil and macrophage membranes with a high-affinity receptor subtype (FPR1) and with a low-affinity subtype FPRL1, promoting a chemotactic response, superoxide anion production, and degranulation. Bacterial colonization of the lower respiratory tract and lung cell damage may represent further sources of formyl peptides in patients withCOPD.Weinvestigated the role of FPRinamousemodelonlunginflammationandemphysema induced by CS. Here, we report the novel observation that genetic ablation of the FPR1 gene (Fpr1) confers protection fromsmoking-induced lung emphysema in mice. Compared with wild-type mice, Fpr1 knockout mice displayed marked decreases in the lung migration of neutrophils and macrophages after CS exposure. Upon transgenic approach, the changes in cell numbers were accompanied by marked modulation of the expression of genes implicated in the inflammatory response. Administration of the FPR1 antagonist cyclosporineH to wild-type mice attenuated the acute inflammatory response evoked by CS. These findings may have clinical significance because current smokers and subjects with emphysema showed increased FPR expression in bronchoalveolar fluids and on peripheral neutrophils. Modulating the FPR1 signal should be explored as a potential new therapy.
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|Titolo:||Genetic Ablation of the Fpr1 Gene Confers Protection from Smoking-Induced Lung Emphysema in Mice|
|Citazione:||Cardini, S., Dalli, J., Fineschi, S., Perretti, M., Lungarella, G., & Lucattelli, M. (2012). Genetic Ablation of the Fpr1 Gene Confers Protection from Smoking-Induced Lung Emphysema in Mice. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 47(3), 332-339.|
|Appare nelle tipologie:||1.1 Articolo in rivista|