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

Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release.
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DOI:
10.1016/j.cub.2013.01.058
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发表时间:
2013-03-04
期刊:
影响因子:
9.2
通讯作者:
Wood, Will
Wood, Will
中科院分区:
生物学1区
文献类型:
--
作者:
Razzell, William;Evans, Iwan Robert;Martin, Paul;Wood, Will

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一个关键的早期伤口反应是由受损组织释放的危险信号所吸引的炎症细胞的招募。过氧化氢(H_2O_2)最近被确定为果蝇胚胎和斑马鱼幼体中最早的伤口诱导剂。过氧化氢信号是通过激活NADPH氧化酶DUOX产生的,因此,第一批炎症细胞在几分钟内就被招募到伤口。到目前为止,还不知道创伤是如何激活DUOX的。在这里,我们展示了激光对果蝇胚胎表皮的损伤触发了瞬间的钙闪光,它以波的形式通过缝隙连接在离伤口边缘几行的细胞中传播。阻断这种钙闪光会抑制伤口部位的过氧化氢释放,并导致迁移到伤口的免疫调节细胞数量减少。我们认为,创伤诱导的钙闪光通过EF手部钙结合基序激活DUOX,从而触发引诱剂损伤提示H_2O_2的产生。因此,钙是创面炎症反应中最早的信号。►损伤果蝇胚胎表皮导致细胞内快速钙波►阻断钙反应导致伤口血细胞减少►DUOX的EF手域是解释创伤诱导的钙闪光所必需的
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. ► Wounding the Drosophila embryo epidermis leads to a rapid intracellular Ca2+ wave ► Blocking the Ca2+ response leads to reduced H2O2 and hemocytes at wounds ► DUOX’s EF hand domain is indispensible to interpret wound-induced Ca2+ flashes
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