Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow

Ulrich Y. Schaff, Neha Dixit, Emily Procyk, Itsukyo Yamayoshi, Tiffany Tse, Scott I. Simon

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Orai1 was reported to function as a calcium channel subunit that facilitates store operated calcium entry (SOCE) in T cells and is necessary for formation of the immune synapse.We reasoned that SOCE via Orai1 might regulate PMNs activation during recruitment to inflamed endothelium. Orai1 function was assessed by real-time imaging of calcium transients as PMNs were stimulated to roll, arrest, and migrate on E-selectin and ICAM-1 in shear flow. Calcium entry was significantly reduced when Orai1 function was impaired by heterozygous knockout in a mouse model or by siRNA knockdown in HL-60 cells. Reduced Orai-1 expression correlated with the delayed onset of arrest and reduced ability to transition to a polarized migratory phenotype. Inhibition of SOCE by treatment with 2-APB, or blocking phospholipase C (PLC) mediated calcium store release with U73122, abrogated formyl peptide induced calcium elevation, and delayed subsequent cell arrest and polarization. These results suggest that calcium entry via Orai1 is the predominant SOCE that cooperates with cytoplasmic calcium store release in coordinating integrin-dependent PMN arrest and migration in the acute response to inflammation.

Original languageEnglish (US)
Pages (from-to)657-666
Number of pages10
JournalBlood
Volume115
Issue number3
DOIs
StatePublished - Jan 21 2010

Fingerprint

Neutrophil Infiltration
Shear flow
Polarization
Calcium
E-Selectin
T-cells
HL-60 Cells
Type C Phospholipases
Intercellular Adhesion Molecule-1
Calcium Channels
Integrins
Synapses
Small Interfering RNA
Endothelium
Chemical activation
Inflammation
T-Lymphocytes
Phenotype
Imaging techniques
Peptides

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow. / Schaff, Ulrich Y.; Dixit, Neha; Procyk, Emily; Yamayoshi, Itsukyo; Tse, Tiffany; Simon, Scott I.

In: Blood, Vol. 115, No. 3, 21.01.2010, p. 657-666.

Research output: Contribution to journalArticle

Schaff, UY, Dixit, N, Procyk, E, Yamayoshi, I, Tse, T & Simon, SI 2010, 'Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow', Blood, vol. 115, no. 3, pp. 657-666. https://doi.org/10.1182/blood-2009-05-224659
Schaff, Ulrich Y. ; Dixit, Neha ; Procyk, Emily ; Yamayoshi, Itsukyo ; Tse, Tiffany ; Simon, Scott I. / Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow. In: Blood. 2010 ; Vol. 115, No. 3. pp. 657-666.
@article{2324b3ad7cea446a8e3315d36093fb6f,
title = "Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow",
abstract = "Orai1 was reported to function as a calcium channel subunit that facilitates store operated calcium entry (SOCE) in T cells and is necessary for formation of the immune synapse.We reasoned that SOCE via Orai1 might regulate PMNs activation during recruitment to inflamed endothelium. Orai1 function was assessed by real-time imaging of calcium transients as PMNs were stimulated to roll, arrest, and migrate on E-selectin and ICAM-1 in shear flow. Calcium entry was significantly reduced when Orai1 function was impaired by heterozygous knockout in a mouse model or by siRNA knockdown in HL-60 cells. Reduced Orai-1 expression correlated with the delayed onset of arrest and reduced ability to transition to a polarized migratory phenotype. Inhibition of SOCE by treatment with 2-APB, or blocking phospholipase C (PLC) mediated calcium store release with U73122, abrogated formyl peptide induced calcium elevation, and delayed subsequent cell arrest and polarization. These results suggest that calcium entry via Orai1 is the predominant SOCE that cooperates with cytoplasmic calcium store release in coordinating integrin-dependent PMN arrest and migration in the acute response to inflammation.",
author = "Schaff, {Ulrich Y.} and Neha Dixit and Emily Procyk and Itsukyo Yamayoshi and Tiffany Tse and Simon, {Scott I.}",
year = "2010",
month = "1",
day = "21",
doi = "10.1182/blood-2009-05-224659",
language = "English (US)",
volume = "115",
pages = "657--666",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow

AU - Schaff, Ulrich Y.

AU - Dixit, Neha

AU - Procyk, Emily

AU - Yamayoshi, Itsukyo

AU - Tse, Tiffany

AU - Simon, Scott I.

PY - 2010/1/21

Y1 - 2010/1/21

N2 - Orai1 was reported to function as a calcium channel subunit that facilitates store operated calcium entry (SOCE) in T cells and is necessary for formation of the immune synapse.We reasoned that SOCE via Orai1 might regulate PMNs activation during recruitment to inflamed endothelium. Orai1 function was assessed by real-time imaging of calcium transients as PMNs were stimulated to roll, arrest, and migrate on E-selectin and ICAM-1 in shear flow. Calcium entry was significantly reduced when Orai1 function was impaired by heterozygous knockout in a mouse model or by siRNA knockdown in HL-60 cells. Reduced Orai-1 expression correlated with the delayed onset of arrest and reduced ability to transition to a polarized migratory phenotype. Inhibition of SOCE by treatment with 2-APB, or blocking phospholipase C (PLC) mediated calcium store release with U73122, abrogated formyl peptide induced calcium elevation, and delayed subsequent cell arrest and polarization. These results suggest that calcium entry via Orai1 is the predominant SOCE that cooperates with cytoplasmic calcium store release in coordinating integrin-dependent PMN arrest and migration in the acute response to inflammation.

AB - Orai1 was reported to function as a calcium channel subunit that facilitates store operated calcium entry (SOCE) in T cells and is necessary for formation of the immune synapse.We reasoned that SOCE via Orai1 might regulate PMNs activation during recruitment to inflamed endothelium. Orai1 function was assessed by real-time imaging of calcium transients as PMNs were stimulated to roll, arrest, and migrate on E-selectin and ICAM-1 in shear flow. Calcium entry was significantly reduced when Orai1 function was impaired by heterozygous knockout in a mouse model or by siRNA knockdown in HL-60 cells. Reduced Orai-1 expression correlated with the delayed onset of arrest and reduced ability to transition to a polarized migratory phenotype. Inhibition of SOCE by treatment with 2-APB, or blocking phospholipase C (PLC) mediated calcium store release with U73122, abrogated formyl peptide induced calcium elevation, and delayed subsequent cell arrest and polarization. These results suggest that calcium entry via Orai1 is the predominant SOCE that cooperates with cytoplasmic calcium store release in coordinating integrin-dependent PMN arrest and migration in the acute response to inflammation.

UR - http://www.scopus.com/inward/record.url?scp=77449102708&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77449102708&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-05-224659

DO - 10.1182/blood-2009-05-224659

M3 - Article

C2 - 19965684

AN - SCOPUS:77449102708

VL - 115

SP - 657

EP - 666

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -