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Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release

Razzell, William, Evans, Iwan Robert, Martin, Paul and Wood, Will 2013. Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release. Current Biology 23 (5) , pp. 424-429. 10.1016/j.cub.2013.01.058

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Abstract

A crucial early wound response is the recruitment of inflammatory cells drawn by danger cues released by the damaged tissue. Hydrogen peroxide (H2O2) has recently been identified as the earliest wound attractant in Drosophila embryos and zebrafish larvae [ 1 and 2]. The H2O2 signal is generated by activation of an NADPH oxidase, DUOX, and as a consequence, the first inflammatory cells are recruited to the wound within minutes. To date, nothing is known about how wounding activates DUOX. Here, we show that laser wounding of the Drosophila embryo epidermis triggers an instantaneous calcium flash, which travels as a wave via gap junctions several cell rows back from the wound edge. Blocking this calcium flash inhibits H2O2 release at the wound site and leads to a reduction in the number of immune cells migrating to the wound. We suggest that the wound-induced calcium flash activates DUOX via an EF hand calcium-binding motif and thus triggers the production of the attractant damage cue H2O2. Therefore, calcium represents the earliest signal in the wound inflammatory response.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RM Therapeutics. Pharmacology
Publisher: Cell Press
ISSN: 0960-9822
Last Modified: 04 Jun 2017 05:11
URI: http://orca-mwe.cf.ac.uk/id/eprint/49312

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