199 149

Cited 4 times in

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

Authors
 Hye Min Lim  ;  Heo Woon  ;  Jung Woo Han  ;  Yoshihiro Baba  ;  Tomohiro Kurosaki  ;  Min Goo Lee  ;  Joo Young Kim 
Citation
 Mediators of Inflammation, Vol.2017 : 8158514-8158514, 2017 
Journal Title
 Mediators of Inflammation 
ISSN
 0962-9351 
Issue Date
2017
MeSH
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*
Abstract
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.
Files in This Item:
T201700795.pdf Download
DOI
10.1155/2017/8158514
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
Yonsei Authors
김주영(Kim, Joo Young) ORCID logo https://orcid.org/0000-0003-2623-1491
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154541
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse