title: Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release.
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. 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.
authors: School of Biochemistry, Faculty of Medical and Veterinary Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors: William
authors: W
authors: Razzell
authors: Iwan Robert
authors: IR
authors: Evans
authors: Paul
authors: P
authors: Martin
authors: Will
authors: W
authors: Wood
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D006434:Hemocytes / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C485366:mol protein, Drosophila; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases
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