Alveolar macrophage dynamics in murine lung regeneration.

Alveolar macrophage dynamics in murine lung regeneration.
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DOI:
10.1002/jcp.24009
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发表时间:
2012-09
影响因子:
5.6
通讯作者:
Mentzer, Steven J.
Mentzer, Steven J.
中科院分区:
生物学2区
文献类型:
--
作者:
Chamoto, Kenji;Gibney, Barry C.;Ackermann, Maximilian;Lee, Grace S.;Lin, Miao;Konerding, Moritz A.;Tsuda, Akira;Mentzer, Steven J.

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在大多数哺乳动物物种中,切除一个肺会导致剩余肺的显著代偿性生长。为了探讨肺泡巨噬细胞(AM)对小鼠肺切除术后肺生长的贡献,我们研究了左肺切除术后3,7,14和21天的支气管肺泡灌洗(BAL)衍生的AM。肺切除术后14天,BAL显示AM(CD 45+、CD 11b −、CD 11 c+、F4/80+、Gr-1−)增加3.0倍。BAL-derived细胞的细胞周期流式细胞术显示S+G2期细胞在肺切除术后第3天(11.3± 2.7%)和第7天(12.1± 1.8%)增加。相应地,AM肺切除术后3 - 14天VEGFR 1和MHC II类表达增加。为了研究外周血细胞对AM群体的潜在贡献,对联体小鼠(野生型/GFP)进行左肺切除术。对肺切除术后肺中GFP+细胞的分析表明,到第14天,少于1%的肺泡巨噬细胞群体来源于外周血。最后,AM基因转录表现出显着的转变,从减少转录的血管生成相关的基因在第3天增加转录后7天肺切除术。局部增殖的AM数量增加,结合其生长相关基因的转录,表明AM积极参与肺的代偿性生长。
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.
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