Spatio-temporal localization of vasoactive intestinal peptide and neutral endopeptidase in allergic murine lungs

Vasoactive intestinal peptide (VIP) is a neuropeptide with cytokine properties that is abundant in the lung. VIP null mice exhibit spontaneous airway inflammation and hyperresponsiveness emphasizing VIP's “anti-asthma” potential. Although VIP's impending protective role in the lung has been demonstrated, its localization in the naïve and allergic murine lungs has not. To this aim, we analyzed the availability of VIP and its protease, neutral peptidase (NEP), in naïve and Aspergillus-sensitized and challenged murine lungs after 3, 7, and 14 days. Both VIP and NEP were predominantly localized to the columnar epithelia of the airways in naïve lungs. A marked decrease in VIP occurred in these cells 3 days after allergen challenge. NEP localization in the columnar epithelia decreased after allergen challenge. At day 14, VIP localization in the columnar epithelia and arteriolar smooth muscle increased while NEP localization at these sites remained low. This study provides new insights into the local regulation of VIP in the columnar epithelia of the allergic lung. Its altered availability in the context of allergy provides fresh evidence for the modulation of pulmonary inflammation by VIP.