Calcium Flashes Orchestrate the Wound Inflammatory Response through DUOX Activation and Hydrogen Peroxide Release

William Razzell, Iwan Robert Evans, Paul Martin, Will Wood

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

A crucial early wound response is the recruitment of inflammatory cells drawn by danger cues released by the damaged tissue. Hydrogen peroxide (HO) has recently been identified as the earliest wound attractant in Drosophila embryos and zebrafish larvae [1, 2]. The HO 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 HO 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 HO. Therefore, calcium represents the earliest signal in the wound inflammatory response.
Original languageEnglish
Pages (from-to)424-9
Number of pages6
JournalCurrent Biology
Volume23
Issue number5
DOIs
Publication statusPublished - 7 Feb 2013

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