TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide

Abstract 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...

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Autores principales:	Hassan Morad, Suaib Luqman, Chun-Hsiang Tan, Victoria Swann, Peter A. McNaughton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/30cdafce157949a5a2be906a5b87c6f5
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id	oai:doaj.org-article:30cdafce157949a5a2be906a5b87c6f5
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spelling	oai:doaj.org-article:30cdafce157949a5a2be906a5b87c6f52021-12-02T16:55:45ZTRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide10.1038/s41598-021-88224-52045-2322https://doaj.org/article/30cdafce157949a5a2be906a5b87c6f52021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88224-5https://doaj.org/toc/2045-2322Abstract 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.Hassan MoradSuaib LuqmanChun-Hsiang TanVictoria SwannPeter A. McNaughtonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hassan Morad Suaib Luqman Chun-Hsiang Tan Victoria Swann Peter A. McNaughton TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide
description	Abstract 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.
format	article
author	Hassan Morad Suaib Luqman Chun-Hsiang Tan Victoria Swann Peter A. McNaughton
author_facet	Hassan Morad Suaib Luqman Chun-Hsiang Tan Victoria Swann Peter A. McNaughton
author_sort	Hassan Morad
title	TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide
title_short	TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide
title_full	TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide
title_fullStr	TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide
title_full_unstemmed	TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide
title_sort	trpm2 ion channels steer neutrophils towards a source of hydrogen peroxide
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/30cdafce157949a5a2be906a5b87c6f5
work_keys_str_mv	AT hassanmorad trpm2ionchannelssteerneutrophilstowardsasourceofhydrogenperoxide AT suaibluqman trpm2ionchannelssteerneutrophilstowardsasourceofhydrogenperoxide AT chunhsiangtan trpm2ionchannelssteerneutrophilstowardsasourceofhydrogenperoxide AT victoriaswann trpm2ionchannelssteerneutrophilstowardsasourceofhydrogenperoxide AT peteramcnaughton trpm2ionchannelssteerneutrophilstowardsasourceofhydrogenperoxide
_version_	1718382791411892224

TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide

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