Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Cell Calcium. 2021 Jun;96:102381. doi: 10.1016/j.ceca.2021.102381. Epub 2021 Feb 21.
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 Ca handling differs between them. In our Fura-2 Ca imaging, TGPMs displayed elevated resting Ca levels, increased store Ca contents and facilitated store-operated Ca entry (SOCE) compared with RPMs. The intensified intracellular Ca stores were enriched with major luminal Ca-binding proteins inducibly expressed in TGPMs. The elevated resting Ca level was predominantly maintained by constitutive Ca 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, Ca-dependent K channels efficiently facilitated SOCE by enhancing the Ca driving force in TGPMs. The consolidated cellular Ca handling described may underlie the specialized cell-physiological features of TGPMs, such as vital proliferation, active migration and avid phagocytosis.
在巨噬细胞生物学中,驻留腹腔巨噬细胞(RPM)和巯基醋酸盐诱导的腹腔巨噬细胞(TGPM)一直被用作原代培养模型。尽管 RPM 和 TGPM 之间的细胞钙处理如何不同仍不清楚,但它们表现出明显的形态、功能和代谢特征。在我们的 Fura-2 钙成像中,与 RPM 相比,TGPM 显示出更高的静息钙水平、增加的储存钙含量和促进钙库操纵性钙内流(SOCE)。增强的细胞内钙库富含在 TGPM 中诱导表达的主要腔钙结合蛋白。升高的静息钙水平主要由组成型钙内流维持,可能通过瞬时受体电位(TRP)家族成员 TRPP2、TRPM7 和 TRPA1。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,并与 Orai 通道一起,促进 SOCE。此外,钙依赖性钾通道通过增强 TGPM 中的钙驱动力,有效地促进 SOCE。所描述的整合细胞钙处理可能是 TGPM 的特殊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。