TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 04 2021
29 04 2021
Historique:
received:
12
08
2020
accepted:
31
03
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
25
2
2023
Statut:
epublish
Résumé
Neutrophils must navigate accurately towards pathogens in order to destroy invaders and thus defend our bodies against infection. Here we show that hydrogen peroxide, a potent neutrophil chemoattractant, guides chemotaxis by activating calcium-permeable TRPM2 ion channels and generating an intracellular leading-edge calcium "pulse". The thermal sensitivity of TRPM2 activation means that chemotaxis towards hydrogen peroxide is strongly promoted by small temperature elevations, suggesting that an important function of fever may be to enhance neutrophil chemotaxis by facilitating calcium influx through TRPM2. Chemotaxis towards conventional chemoattractants such as LPS, CXCL2 and C5a does not depend on TRPM2 but is driven in a similar way by leading-edge calcium pulses. Other proposed initiators of neutrophil movement, such as PI3K, Rac and lyn, influence chemotaxis by modulating the amplitude of calcium pulses. We propose that intracellular leading-edge calcium pulses are universal drivers of the motile machinery involved in neutrophil chemotaxis.
Identifiants
pubmed: 33927223
doi: 10.1038/s41598-021-88224-5
pii: 10.1038/s41598-021-88224-5
pmc: PMC8085234
doi:
Substances chimiques
TRPM Cation Channels
0
TRPM2 protein, mouse
0
Hydrogen Peroxide
BBX060AN9V
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9339Subventions
Organisme : Wellcome Trust
ID : 205006/Z/16/Z
Pays : United Kingdom
Références
J Immunol. 2017 May 1;198(9):3679-3689
pubmed: 28363904
Cell Rep. 2015 Dec 15;13(10):2107-17
pubmed: 26673320
Biochim Biophys Acta. 2009 Jun;1793(6):933-40
pubmed: 19010359
Cell. 2007 Apr 6;129(1):220
pubmed: 17418797
Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6745-50
pubmed: 22493272
Curr Opin Genet Dev. 2016 Oct;40:17-22
pubmed: 27266971
Biophys J. 2017 May 9;112(9):2011-2018
pubmed: 28494970
EMBO J. 2006 May 3;25(9):1804-15
pubmed: 16601673
Br J Pharmacol. 2008 Mar;153(6):1324-30
pubmed: 18204483
Nature. 2016 Aug 25;536(7617):460-3
pubmed: 27533035
Nature. 2009 Jun 18;459(7249):996-9
pubmed: 19494811
Nature. 2020 Aug;584(7820):E5-E12
pubmed: 32788732
Science. 2018 Dec 21;362(6421):
pubmed: 30467180
Nat Med. 2008 Jul;14(7):738-47
pubmed: 18542050
J Cell Biol. 1991 Jan;112(1):149-58
pubmed: 1702443
EMBO J. 2005 Dec 21;24(24):4211-23
pubmed: 16319926
Sci Signal. 2016 Aug 16;9(441):ra82
pubmed: 27531651
J Mol Biol. 2003 Sep 12;332(2):385-98
pubmed: 12948489
Dev Cell. 2011 Oct 18;21(4):735-45
pubmed: 22014524
J Immunol. 2007 Dec 1;179(11):7827-39
pubmed: 18025229
Nat Rev Immunol. 2013 Mar;13(3):159-75
pubmed: 23435331
J Gen Physiol. 2018 Apr 2;150(4):521-537
pubmed: 29514865
Physiol Rev. 2016 Oct;96(4):1261-96
pubmed: 27512009
Annu Rev Physiol. 2006;68:619-47
pubmed: 16460286
Int J Surg Pathol. 2007 Jul;15(3):292-6
pubmed: 17652540
Nature. 2001 May 31;411(6837):595-9
pubmed: 11385575
Br J Pharmacol. 2006 Jun;148(3):264-73
pubmed: 16604090
Channels (Austin). 2017 Sep 3;11(5):426-433
pubmed: 28633002
Science. 1991 Nov 1;254(5032):703-6
pubmed: 1948048
Curr Biol. 2010 Mar 9;20(5):464-70
pubmed: 20188558
Cell Calcium. 2011 Sep;50(3):279-87
pubmed: 21616534
Elife. 2016 Jul 06;5:
pubmed: 27383051
Biochem J. 2003 May 1;371(Pt 3):1045-53
pubmed: 12564954
Curr Biol. 2013 Mar 4;23(5):424-9
pubmed: 23394834
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11578-83
pubmed: 21709234
Dev Cell. 2016 Sep 12;38(5):453-62
pubmed: 27569419
J Cell Biol. 2017 Aug 7;216(8):2515-2531
pubmed: 28687663
J Physiol. 2011 Apr 1;589(Pt 7):1515-25
pubmed: 21135052
J Biol Chem. 1985 Mar 25;260(6):3440-50
pubmed: 3838314
Chem Phys Lipids. 2014 Sep;182:73-9
pubmed: 24451847
Curr Biol. 2012 May 8;22(9):837-42
pubmed: 22521790
Dev Cell. 2010 Feb 16;18(2):226-36
pubmed: 20159593
Methods Enzymol. 2013;528:237-55
pubmed: 23849869
Eur J Cell Biol. 1996 Aug;70(4):347-51
pubmed: 8864663
Cardiovasc Res. 2013 Feb 1;97(2):271-81
pubmed: 23129587
Zebrafish. 2016 Aug;13(4):374-5
pubmed: 27058231
J Cell Sci. 1995 Oct;108 ( Pt 10):3199-205
pubmed: 7593281
Curr Biol. 2015 Jun 15;25(12):1606-12
pubmed: 26028435
Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16949-54
pubmed: 25385633
FASEB J. 2011 Oct;25(10):3529-42
pubmed: 21753080
Semin Cell Dev Biol. 2018 Aug;80:13-16
pubmed: 28751250
Nat Med. 1996 Nov;2(11):1259-62
pubmed: 8898757
Sci Signal. 2018 Mar 13;11(521):
pubmed: 29535263
Pflugers Arch. 2018 May;470(5):787-798
pubmed: 29552700
J Biol Chem. 2006 Dec 15;281(50):38748-56
pubmed: 17060318
J Biol Chem. 2010 Sep 24;285(39):30091-102
pubmed: 20650899
Nature. 2011 Nov 20;480(7375):109-12
pubmed: 22101434
Cell. 2002 Mar 8;108(5):595-8
pubmed: 11893331
Biochim Biophys Acta. 2014 May;1840(5):1596-604
pubmed: 24060746