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UDP-Induced Phagocytosis and ATP-Stimulated Chemotactic Migration Are Impaired in STIM1-/- Microglia In Vitro and In Vivo

 Hye Min Lim  ;  Heo Woon  ;  Jung Woo Han  ;  Yoshihiro Baba  ;  Tomohiro Kurosaki  ;  Min Goo Lee  ;  Joo Young Kim 
 MEDIATORS OF INFLAMMATION, Vol.2017 : 8158514, 2017 
Journal Title
Issue Date
Adenosine Triphosphate/pharmacology* ; Animals ; Astrocytes/drug effects ; Astrocytes/metabolism ; Calcium Signaling/drug effects ; Cells, Cultured ; Chemotaxis/drug effects* ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/drug effects* ; Microglia/metabolism* ; Neurons/drug effects ; Neurons/metabolism ; ORAI1 Protein/genetics ; ORAI1 Protein/metabolism ; Phagocytosis/drug effects* ; Stromal Interaction Molecule 1/deficiency* ; Stromal Interaction Molecule 1/genetics ; Uridine Diphosphate/metabolism*
STIM1 is the only currently known intracellular calcium sensor that functions as the calcium influx regulator controlling immune cell activation. STIM1 function in immune cell calcium signalling has been studied extensively; however, its role in microglia, innate immune cells in brain, has not been fully understood. Here, we report that STIM1-/- murine microglia lost store-operated calcium influx and displayed aberrant immunological functions. Microglial functions regulated by chronic and global [Ca2+]i changes were reduced significantly, including cytokine releases and opsonin-dependent phagocytosis. More dramatically, cellular functions governed by Ca2+ regulation in local microdomains at the cell periphery, such as UDP-induced phagocytosis and ATP-stimulated chemotactic migration, were severely reduced in STIM1-/- microglia. Interestingly, UDP-induced Orai1 mobilization to the peripheral region was greatly attenuated in STIM1-/- microglia. Their chemotactic migration defect was reproduced in vivo in embryonic brain; the aggregated number of STIM1-/- microglia in LPS- (lipopolysaccharide-) injected lesions was much smaller than that in wild-type microglia. Furthermore, the neuron phagoptosis activities of activated microglia were significantly diminished in the STIM1-/- microglia. These in vitro and in vivo results suggest that STIM1-mediated store-operated calcium entry is important for the regulation of global [Ca2+]i changes which differentiates into active immune state of microglia, but it is more crucial for the regulation of local [Ca2+] microdomains which mediates the acute motility of murine microglia.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Young(김주영) ORCID logo https://orcid.org/0000-0003-2623-1491
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
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