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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article number8158514
JournalMediators of Inflammation
Volume2017
DOIs
Publication statusPublished - Jan 1 2017

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Uridine Diphosphate
Microglia
Phagocytosis
Adenosine Triphosphate
Calcium
In Vitro Techniques
Opsonin Proteins
Calcium Signaling
Brain
Lipopolysaccharides
Cytokines
Neurons

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology

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UDP-induced phagocytosis and ATP-stimulated chemotactic migration are impaired in STIM1 -/- microglia in vitro and in vivo. / Lim, Hye Min; Woon, Heo; Han, Jung Woo; Baba, Yoshihiro; Kurosaki, Tomohiro; Lee, Min Goo; Kim, Joo Young.

In: Mediators of Inflammation, Vol. 2017, 8158514, 01.01.2017.

Research output: Contribution to journalArticle

Lim, Hye Min ; Woon, Heo ; Han, Jung Woo ; Baba, Yoshihiro ; Kurosaki, Tomohiro ; Lee, Min Goo ; Kim, Joo Young. / UDP-induced phagocytosis and ATP-stimulated chemotactic migration are impaired in STIM1 -/- microglia in vitro and in vivo. In: Mediators of Inflammation. 2017 ; Vol. 2017.
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