STIM2 is the essential STIM protein in non-SOCE calcium responses of macrophages in vitro and in vivo
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1
Hannover Medical School, Clinical Immunology and Rheumatology, Germany
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2
McMaster University, Faculty of health Sciences, Farncombe Family Digestive Health Research Institute, Canada
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3
University Hospital and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Chair of Experimental Biomedicine, Germany
Macrophage physiology critically depends on Ca2+ signalling. STIM isoforms are mediators of the most common mode of calcium influx in non-excitable cells, Store-Operated Ca2+ Entry (SOCE). Here, the relative dependence of key aspects of macrophage physiology on the mobilization of Ca2+ from the internal stores and/or the extracellular compartment was evaluated. Among the functions studied, cytokine responses to TLR ligands and chemokine elicited motility were mainly dependent on the mobilization of intracellular Ca2+. In contrast, FcγR-mediated phagocytosis, apart from internal stores, depends on Ca2+ influx and SOCE. STIM2, in addition to contributing in SOCE, is involved in the maintenance of the internal ER-store of Ca2+. The consequences of STIM2 deficiency in these Ca2+ dependent functions were characterized and contrasted with the effect of STIM1 deficiency. The SOCE dependent FcγR-mediated phagocytosis was reduced in case of STIM2 deficiency. However, the resulting defect was smaller as compared to the consequences of STIM1 deficiency. Moreover, genetic deletion of STIM2 had no effect on the phagocytosis-promoting function of C5a in vitro and in a model of autoimmune hemolytic anemia in vivo. Effective cytokine production downstream of TLRs and elicited motility, however, strictly depends on the presence of STIM2. In vivo, Stim2-/- mice exhibited milder LPS-induced sepsis and thioglycollate-elicited peritonitis. Interestingly, none of these SOCE-independent functions were reduced in case of STIM1 deficiency, suggesting their being specifically mediated by STIM2.
Acknowledgements
Funded by the DFG and the International HRBS PhD program in Molecular Medicine.
Keywords:
STIM1,
STIM2,
SOCE,
Calcium,
Macrophages,
Fcgamma receptors,
LPS,
C5a,
CCL2,
MCP1,
Chemotaxis,
Migration
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Sogkas
G,
Syed
S,
Rau
E,
Stegner
D,
Vögtle
T,
Nieswandt
B,
Schmidt
R and
Gessner
J
(2013). STIM2 is the essential STIM protein in non-SOCE calcium responses of macrophages in vitro and in vivo.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00444
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Received:
02 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Georgios Sogkas, Hannover Medical School, Clinical Immunology and Rheumatology, Hannover, Germany, sogkas.georgios@mh-hannover.de
Prof. Johannes Engelbert Gessner, Hannover Medical School, Clinical Immunology and Rheumatology, Hannover, Germany, Gessner.Johannes@mh-hannover.de