Adrenomedullin regenerates alveoli and vasculature in elastase-induced pulmonary emphysema in mice.

Rationale: Adrenomedullin, a potent vasodilator peptide, regulates cell growth and survival. However, whether adrenomedullin contributes to lung regeneration remains unknown. Objectives: To investigate whether adrenomedullin influences the kinetics of bone marrow cells, and whether adrenomedullin promotes regeneration of alveoli and vasculature and thereby improves lung structure and function in elastase-induced emphysema in mice. Methods: Adrenomedullin or vehicle was randomly administered to C57BL/6 mice for 5 days. We counted the numbers of mononuclear cells and stem cell antigen-1–positive cells in circulating blood. After intratracheal injection of elastase or saline, mice were randomized to receive continuous infusion of adrenomedullin or vehicle for 14 days. Functional and histologic analyses were performed 28 days after treatment.Results:Twenty-eightdaysafterelastaseinjection,destruction of the alveolar walls was observed. However, adrenomedullin infusion significantly inhibited the increase in lung volume, static lung compliance, and mean linear intercept in mice given elastase. Adrenomedullin increased the numbers of mononuclear cells and stem cell antigen-1–positive cells in circulating blood. Adrenomedullin significantly increased the number of bone marrow–derived cells incorporated into the elastase-treated lung. Some of these cells were positive for cytokeratin or von Willebrand factor. Infusion of adrenomedullin after the establishment of emphysema also had beneficial effects on lung structure and function. In vitro, addition ofadrenomedullinattenuateselastase-inducedcelldeathinalveolar