Enhanced Ca2+ handling in thioglycolate-elicited peritoneal macrophages

Abstract

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.

Keywords: Ca(2+)-dependent K(+) channel; Constitutive Ca(2+) influx; Intracellular Ca(2+) stores; Luminal Ca(2+)-binding protein; Phospholipase C; Store-operated Ca(2+) entry; TRPA1 channel; TRPM7 channel; TRPP2 channel.