Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS One. 2011;6(11):e26716. doi: 10.1371/journal.pone.0026716. Epub 2011 Nov 16.
Angiogenesis after pulmonary ischemia is initiated by reactive O(2) species and is dependent on CXC chemokine growth factors, and its magnitude is correlated with the number of lavaged macrophages. After complete obstruction of the left pulmonary artery in mice, the left lung is isolated from the peripheral circulation until 5-7 days later, when a new systemic vasculature invades the lung parenchyma. Consequently, this model offers a unique opportunity to study the differentiation and/or proliferation of monocyte-derived cells within the lung. In this study, we questioned whether macrophage subpopulations were differentially expressed and which subset contributed to growth factor release. We characterized the change in number of all macrophages (MHCII(int), CD11C+), alveolar macrophages (MHCII(int), CD11C+, CD11B-) and mature lung macrophages (MHCII(int), CD11C+, CD11B+) in left lungs from mice immediately (0 h) or 24 h after left pulmonary artery ligation (LPAL). In left lung homogenates, only lung macrophages increased 24 h after LPAL (vs. 0 h; p<0.05). No changes in proliferation were seen in any subset by PCNA expression (0 h vs. 24 h lungs). When the number of monocytic cells was reduced with clodronate liposomes, systemic blood flow to the left lung 14 days after LPAL decreased by 42% (p<0.01) compared to vehicle controls. Furthermore, when alveolar macrophages and lung macrophages were sorted and studied in vitro, only lung macrophages secreted the chemokine MIP-2α (ELISA). These data suggest that ischemic stress within the lung contributes to the differentiation of immature monocytes to lung macrophages within the first 24 h after LPAL. Lung macrophages but not alveolar macrophages increase and secrete the proangiogenic chemokine MIP-2α. Overall, an increase in the number of lung macrophages appears to be critical for neovascularization in the lung, since clodronate treatment decreased their number and attenuated functional angiogenesis.
肺缺血后的血管生成由活性氧（O2）物种启动，依赖于 CXC 趋化因子生长因子，其程度与灌洗的巨噬细胞数量相关。在小鼠左肺动脉完全阻塞后，将左肺与外周循环隔离，直到 5-7 天后，新的全身脉管系统侵入肺实质。因此，该模型提供了一个独特的机会来研究单核细胞衍生细胞在肺内的分化和/或增殖。在这项研究中，我们质疑巨噬细胞亚群是否存在差异表达，以及哪个亚群有助于生长因子的释放。我们研究了左肺中所有巨噬细胞（MHCII(int)，CD11C+）、肺泡巨噬细胞（MHCII(int)，CD11C+，CD11B-）和成熟肺巨噬细胞（MHCII(int)，CD11C+，CD11B+）的数量在左肺动脉结扎（LPAL）后立即（0 小时）或 24 小时的变化。在左肺匀浆中，只有肺巨噬细胞在 LPAL 后 24 小时增加（与 0 小时相比；p<0.05）。PCNA 表达显示任何亚群的增殖均无变化（0 小时与 24 小时的肺）。用氯膦酸盐脂质体减少单核细胞数量后，LPAL 后 14 天左肺的全身血流减少了 42%（p<0.01）与载体对照相比。此外，当肺泡巨噬细胞和肺巨噬细胞被分选并在体外研究时，只有肺巨噬细胞分泌趋化因子 MIP-2α（ELISA）。这些数据表明，LPAL 后最初 24 小时内，肺内的缺血应激导致未成熟单核细胞分化为肺巨噬细胞。肺巨噬细胞而不是肺泡巨噬细胞增加并分泌促血管生成趋化因子 MIP-2α。总的来说，肺巨噬细胞数量的增加似乎对肺内新生血管形成至关重要，因为氯膦酸盐处理减少了它们的数量并减弱了功能性血管生成。
