Alveolar Macrophage Dynamics in Murine Lung Regeneration

In most mammalian species, the removal of one lung results in dramatic compensatory growth of the remaining lung. To investigate the contribution of alveolar macrophages (AM) to murine post-pneumonectomy lung growth, we studied bronchoalveolar lavage (BAL)-derived AM on 3, 7, 14 and 21 days after left pneumonectomy. BAL demonstrated a 3.0-fold increase in AM (CD45+, CD11b−, CD11c+, F4/80+, Gr-1− ) by 14 days after pneumonectomy. Cell cycle flow cytometry of the BAL-derived cells demonstrated an increase in S+G2 phase cells on days 3 (11.3± 2.7 %) and 7 (12.1±1.8 %) after pneumonectomy. Correspondingly, AM demonstrated increased expression of VEGFR1 and MHC class II between days 3 and 14 after pneumonectomy. To investigate the potential contribution of peripheral blood cells to this AM population, parabiotic mice (wild-type/GFP) underwent left pneumonectomy. Analysis of GFP+ cells in the post-pneumonectomy lung demonstrated that by day 14, less than 1% of the alveolar macrophage population were derived from the peripheral blood. Finally, AM gene transcription demonstrated a significant shift from decreased transcription of angiogenesis-related genes on day 3 to increased transcription on day 7 after pneumonectomy. The increased number of locally proliferating AM, combined with their growth-related gene transcription, suggests that AM actively participate in compensatory lung growth.