Enhanced Ca2+ handling in thioglycolate-elicited peritoneal macrophages
Enhanced Ca2+ handling in thioglycolate-elicited peritoneal macrophages
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DOI：
10.1016/j.ceca.2021.102381
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发表时间：
2021-02-26
期刊：
影响因子：
4
通讯作者：
Takeshima, Hiroshi
中科院分区：
文献类型：
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作者：
Liu, Feng;Xu, Luxin;Takeshima, Hiroshi
在巨噬细胞生物学中，常驻腹膜巨噬细胞（RPM）和巯基乙酸盐诱导的腹膜巨噬细胞（TGPMs）传统上被用作原代培养模型。RPMs和TGPMs表现出不同的形态，功能和代谢特征，尽管目前还不清楚它们之间的细胞Ca 2+处理有何不同。在我们的Fura-2 Ca 2+成像中，与RPM相比，TGPMs显示静息Ca 2+水平升高，钙库Ca 2+含量增加，并促进钙库操作的Ca 2+内流（SOCE）。强化的细胞内Ca 2+商店丰富的主要管腔Ca 2+结合蛋白诱导表达TGPMs。升高的静息Ca 2+水平主要由组成性Ca 2+内流维持，可能通过瞬时受体电位（TRP）家族成员TRPP 2、TRPM 7和TRPA 1。这些TRP家族通道似乎主要以依赖于磷脂酶C活性的方式被激活，并且与奥赖通道一起促成SOCE。此外，Ca 2+依赖性K+通道通过增强TGPMs中的Ca 2+驱动力而有效地促进了SOCE。所描述的巩固的细胞Ca 2+处理可能是TGPMs的专门细胞生理特征的基础，例如重要的增殖、活跃的迁移和贪婪的吞噬作用。
In macrophage biology, resident peritoneal macrophages (RPMs) and thioglycolate-elicited peritoneal macrophages (TGPMs) have been traditionally utilized as primary cultured models. RPMs and TGPMs exhibit distinct morphological, functional and metabolic characteristics, although it remains unclear how cellular Ca2+ handling differs between them. In our Fura-2 Ca2+ imaging, TGPMs displayed elevated resting Ca2+ levels, increased store Ca2+ contents and facilitated store-operated Ca2+ entry (SOCE) compared with RPMs. The intensified intracellular Ca2+ stores were enriched with major luminal Ca2+-binding proteins inducibly expressed in TGPMs. The elevated resting Ca2+ level was predominantly maintained by constitutive Ca2+ influx, probably through the transient receptor potential (TRP) family members TRPP2, TRPM7 and TRPA1. These TRP family channels seemed to be largely activated in a manner dependent on phospholipase C activity, and together with Orai channels, contributed to SOCE. Moreover, Ca2+-dependent K+ channels efficiently facilitated SOCE by enhancing the Ca2+ driving force in TGPMs. The consolidated cellular Ca2+ handling described may underlie the specialized cell-physiological features of TGPMs, such as vital proliferation, active migration and avid phagocytosis.