The prolonged life-span of alveolar macrophages

The prolonged life-span of alveolar macrophages
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DOI:
10.1165/rcmb.2007-0224rc
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发表时间:
2008-04-01
影响因子:
6.4
通讯作者:
Fine, Alan
Fine, Alan
中科院分区:
医学1区
文献类型:
--
作者:
Murphy, Jaime;Summer, Ross;Fine, Alan

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为了进一步检查肺泡巨噬细胞的半衰期,通过供体CD 45.1细胞的骨髓移植产生嵌合CD 45.2小鼠。在给予供体细胞之前,受体小鼠被分成两组:第一组接受全身照射;第二组也接受照射,但是胸部、头部和上肢用铅屏蔽。然后对血液、腹膜和支气管肺泡灌洗液细胞随时间进行流式细胞术分析,以定量植入。未屏蔽组小鼠产生的数据显示巨噬细胞半衰期为30天。然而,在屏蔽队列中,我们发现到8个月时,尽管供体骨髓重建了血液和腹膜,但供体细胞对受体肺泡巨噬细胞的替代可以忽略不计。与这些发现一致,肺泡巨噬细胞的平均荧光强度在体内PKH 26染料负载后4周内保持稳定。总之,这些数据表明,先前的肺泡巨噬细胞半衰期研究被以下事实混淆,即它们没有考虑辐射预处理方案的毒性作用,并证明骨髓在稳态条件下对肺泡巨噬细胞室没有显著贡献。
To further examine the half-life of alveolar macrophages, chimeric CD 45.2 mice were generated through bone marrow transplantation of donor CD 45.1 cells. Before administration of donor cells, recipient mice were divided into two cohorts: the first cohort received total body irradiation; the second cohort also received irradiation-however, the thorax, head, and upper extremities were shielded with lead. Flow cytometric analysis was then performed on blood, peritoneal, and bronchoalveolar lavage cells over time to quantify engraftment. The data generated for the unshielded cohort of mice revealed a macrophage half-life of 30 days. In the shielded cohort, however, we found that by 8 months there was negligible replacement of recipient alveolar macrophages by donor cells, despite reconstitution of the blood and peritoneum by donor bone marrow. Consistent with these findings, the mean fluorescent intensity of alveolar macrophages remained stable over a 4-week period after in vivo PKH26 dye loading. Together, these data show that previous alveolar macrophage half-life studies were confounded by the fact that they did not account for the toxic effects of irradiation conditioning regimens, and demonstrate that the bone marrow does not significantly contribute to the alveolar macrophage compartment during steady-state conditions.