Intratracheal f-MLP administration in mice reproduces smoke-induced pulmonary changes

Mucus hypersecretion and emphysema are important hallmarks of chronic obstructive lung disease. These changes may be induced in mice by chronic exposure to cigarette smoke (CS), however a different degree of sensitivity is observed in different strains of mice. In particular, C57Bl/6J mice, which are moderately deficient in serum alpha1-PI and sensitive to oxidants, develop after CS both goblet cell metaplasia (GCM) and emphysema, whereas DBA/2 mice, which are sensitive to oxidants, develop only emphysematous lesions. In previous studies we showed that the acute inflammatory effect induced by CS can be mimicked in C57BL/6J mice by i.tr. instillation of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), a neutrophil chemotactic peptide. In this study we compared the pulmonary changes induced by fMLP in C57Bl/6J and DBA/2 mice. At 7 and 21days after a single administration of fMLP (200 mg), both strains developed pulmonary emphysema, but GCM appeared only in C57Bl/6J mice. Thus, in these strains pulmonary changes similar to those observed after CS can be elicited by fMLP administration. Strain characteristics (such as alpha1-PI levels, sensitivity to oxidants) and pheno- typical responses (apoptosis and cytokine distribution) may condition parenchymal and airway changes in response to fMLP. The knowledge of the interstrain variation in the lung response to fMLP may important for investigating the role of single factors in the pathogenesis of COPD. This model may be also useful for studying potential therapeutic agents.