The phenotype of peritoneal mouse macrophages depends on the mitochondria and ATP/ADP homeostasis
The phenotype of peritoneal mouse macrophages depends on the mitochondria and ATP/ADP homeostasis
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DOI：
10.1016/j.cellimm.2017.11.003
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发表时间：
2018-02-01
影响因子：
4.3
通讯作者：
Kloc, Malgorzata
中科院分区：
文献类型：
--
作者：
Chen, Wei;Sandoval, Hector;Kloc, Malgorzata
不同的巨噬细胞亚型具有不同的形态/形状和功能。幼稚M0巨噬细胞是细长的。产生杀菌分子iNos的促炎性M1是圆形的。产生促愈合酶Arg-1的抗炎M2巨噬细胞高度伸长。我们以前表明，M0和M2的形态，而不是M1巨噬细胞是RhoA依赖性的。RhoA的巨噬细胞特异性缺失导致M0和M2而不是M1巨噬细胞的极端伸长（蜂鸟表型）。M1和M2巨噬细胞的代谢状态也不同。在这里，我们研究了氧化磷酸化抑制剂，抗霉素A和寡霉素A，在次优剂量，去极化线粒体，但不消除线粒体功能，对野生型和RhoA缺失的M0，M1和M2小鼠腹腔巨噬细胞的线粒体/能量产生和表型的影响。我们发现，虽然未处理的M1巨噬细胞具有最低的ATP水平，而M2具有最高的ATP水平，但M0、M1和M2巨噬细胞之间的ATP/ADP比率几乎相同。抑制剂处理导致M0和M2巨噬细胞中ATP水平和ATP/ADP比值增加约60%，丝状（F）肌动蛋白水平降低，这些变化与M0和M2巨噬细胞的急剧缩短/尾部收缩以及M2巨噬细胞中Arg-1表达降低相关。M1巨噬细胞的处理仅导致ATP水平和ATP/ADP比率增加30%，虽然它不影响M1巨噬细胞的形状，但它增加了iNos的产生。这表明小鼠巨噬细胞表型的维持依赖于线粒体功能和ATP/ADP稳态。
Different macrophage subtypes have different Morphologies/shapes and functions. Naive M0 macrophages are elongated. Pro-inflammatory M1 that produce the bactericidal Molecule iNos are round. Anti-inflammatory M2 macrophages that produce the pro-healing enzyme Arg-1 are highly elongated. We showed previously that the Morphologies of M0 and M2 but not M1 macrophages are RhoA-dependent. Macrophage-specific deletion of RhoA causes the extreme elongation (hummingbird phenotype) of M0 and M2 but not M1 macrophages. The M1 and M2 macrophages also differ in their metabolic status. Here, we studied the effect of the oxidative phosphorylation inhibitors, antimycin A and oligomycin A, at a suboptimal dose, which depolarizes mitochondria but does not eliminate mitochondrial functions, on the mitochondria/energy production and phenotype of wild-type and RhoA-deleted M0, M1 and M2 peritoneal Mouse macrophages. We found that, while untreated M1 macrophages had the lowest and the M2 had the highest level of ATP the ATP/ADP ratio was nearly identical between M0, M1 and M2 macrophages. Inhibitor treatment resulted in approximately 60% increase in ATP level and ATP/ADP ratio in M0 and M2 macrophages, and decrease in the level of filamentous (F) actin, and these changes correlated with a drastic shortening/tail retraction of M0 and M2 macrophages, and decreased expression of Arg-1 in M2 macrophages. The treatment of M1 macrophages caused only a 30% increase in the ATP level and ATP/ADP ratio, and while it did not affect the shape of M1 macrophages, it increased the production of iNos. This indicates that the maintenance of Mouse macrophage phenotypes depends on mitochondrial function and ATP/ADP homeostasis.