Enhanced Ca2+ handling in thioglycolate-elicited peritoneal macrophages

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.