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Cooperative and alternate functions for STIM1 and STIM2 in macrophage activation and in the context of inflammation.


ABSTRACT: Calcium (Ca(2+)) signaling in immune cells, including macrophages, controls a wide range of effector functions that are critical for host defense and contribute to inflammation and autoimmune diseases. However, receptor-mediated Ca(2+) responses consist of complex mechanisms that make it difficult to identify the pathogenesis and develop therapy. Previous studies have revealed the importance of the Ca(2+) sensor STIM1 and store-operated Ca(2+)-entry (SOCE) for Fc?-receptor activation and IgG-induced inflammation. Here, we identify the closely related STIM2 as mediator of cell migration and cytokine production downstream of GPCR and TLR4 activation in macrophages and show that mice lacking STIM2 are partially resistant to inflammatory responses in peritonitis and LPS-induced inflammation. Interestingly, STIM2 modulates the migratory behavior of macrophages independent from STIM1 and without a strict requirement for Ca(2+) influx. While STIM2 also contributes in part to Fc?R activation, the C5a-induced amplification of IgG-mediated phagocytosis is mainly dependent on STIM1. Blockade of STIM-related functions limits mortality in experimental models of AIHA and LPS-sepsis in normal mice. These results suggest benefits of Ca(2+)-inhibition for suppression of exacerbated immune reactions and illustrate the significance of alternate functions of STIM proteins in macrophage activation and in the context of innate immune inflammation.

SUBMITTER: Sogkas G 

PROVIDER: S-EPMC4578517 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Cooperative and alternate functions for STIM1 and STIM2 in macrophage activation and in the context of inflammation.

Sogkas Georgios G   Stegner David D   Syed Shahzad N SN   Vögtle Timo T   Rau Eduard E   Gewecke Britta B   Schmidt Reinhold E RE   Nieswandt Bernhard B   Gessner Johannes Engelbert JE  

Immunity, inflammation and disease 20150512 3


Calcium (Ca(2+)) signaling in immune cells, including macrophages, controls a wide range of effector functions that are critical for host defense and contribute to inflammation and autoimmune diseases. However, receptor-mediated Ca(2+) responses consist of complex mechanisms that make it difficult to identify the pathogenesis and develop therapy. Previous studies have revealed the importance of the Ca(2+) sensor STIM1 and store-operated Ca(2+)-entry (SOCE) for Fcγ-receptor activation and IgG-ind  ...[more]

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