INTRODUCTION: Cigarette smoke (CS) is the main causative factor of COPD in man. Morphological features of COPD including emphysema
and chronic bronchitis associated with mucus hypersecretion can be induced in mice by chronic CS exposure. The peptide fMLP
(N-formyl-L-methionyl-L-leucyl-L-phenylalanine) is an active component of cigarette smoke (CS). fMLP interacts on the neutrophil and
macrophage membranes with a high-affinity receptor subtype (FPR) and with a low-affinity subtype FPRL1 promoting a chemotactic
response, superoxide anion production and degranulation. fMLP-receptors are found to be increased in the lavage fluids from cigarette
smokers and subjects with COPD. To date, the role of FPRs in COPD remains poorly understood. We examined whether FPR contributes to
lung damage induced by CS, by comparing the response of FPR knockout (Fpr1-/-) mice with that of wild-type (WT) C57 Bl/6 mice.
METHODS and RESULTS: After chronic exposure to CS (3 cigarettes/day, 5 days/week for 7 months) WT mice showed significant foci of
emphysema disseminated throughout the lung parenchyma with a significant increase of the mean linear intercept (+ 21 %) and a
decrease of the internal surface area (– 13 %). Air-control groups and smoke exposed Fpr1-/- mice showed no areas of emphysema.
Acute smoke exposure (5 cigarettes/day, for 3 days) caused in WT mice a 3,7 fold and a 1,3 fold increase in BALF neutrophils and
macrophages, respectively. Fpr1 ablation in mice prevented after CS exposure the increase of neutrophils and macrophages by 73 and
42%, respectively. CONCLUSIONS: This study supports a role for FPR signalling in the development of CS-induced emphysema
