Localization of the peptide transporter PEPT2 in the lung - Implications for pulmonary oligopeptide uptake

Pulmonary delivery of peptidomimetic antibiotics is frequently used for loc al drug therapy in pulmonary infections. Identification of transport pathwa ys into airway epithelia can lead to new strategies of therapy. Here we des cribe the distribution of the beta -lactam-transporting high-affinity proto n-coupled peptide transporter PEPT2 in mammalian lungs. Using reverse trans criptase-polymerase chain reaction and Northern blot analysis, PEPT2-mRNA w as detected in lung extracts. The expression of PEPT2-mRNA and protein was localized to alveolar type II pneumocytes, bronchial epithelium, acid endot helium of small arteries of rat lung by nonisotopic in situ hybridization a nd immunohistochemistry. In addition, transport studies using murine whole- organ preparations revealed transporter-mediated uptake of a fluorophore-co njugated dipeptide derivative into bronchial epithelial cells and type II p neumocytes. This transport was competitively inhibited by cephalosporins an d dipeptides that are reported as PEPT2-carried substrates. Cell specificit y of the PEPT2-mediated uptake pattern was confirmed by double labeling wit h Lycopersicon esculentum lectin. Together these data suggest that PEPT2 is the molecular basis for the transport of peptides and peptidomimetics in p ulmonary epithelial cells. In conclusion PEPT2 may be an interesting target for pulmonary delivery of peptides and peptidomimetics.