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Alveolar macrophage dynamics in murine lung regeneration

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Abstract

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 (AMs) 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 AM 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. J. Cell. Physiol. 227: 3208–3215, 2012. © 2011 Wiley Periodicals, Inc.

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