Curr Biol：应对损伤的炎症反应信号被关闭的确切机制

莫纳什大学与澳大利亚再生医学研究所（ARMI）的研究人员发表在Current Biology杂志上的一项新研究详细介绍了机体关闭触发人体应对损伤的初始炎症反应信号的确切机制。

当身体出现伤口或被擦伤时，白血细胞又称白细胞会到达损伤部位，保护组织免受感染，并开始修复损坏组织。然而，这一时期的炎症反应只是暂时的。如果身体允许炎症反应持续时间过长，那么下一阶段的愈合效果就会被大打折扣。

早期研究确定了募集白细胞到损伤部位的初始信号，但这种早期信号是如何被关闭的，又是如何使得白细胞不再发挥作用仍是未知的。最新的研究结果显示，一种叫做髓过氧化物酶的酶是这一过程的关键。

该小组研究了用不同荧光颜色标记斑马鱼的白细胞和组织，使白细胞的运动以及化学信号浓度能被同时监控。

在显微镜下观察微小的、透明的斑马鱼时，研究人员能够观察到单个白血细胞，明确了白细胞是如何调节炎症期的愈合过程的。

研究员Graham Lieschke教授说：研究结果表明白血细胞的活动对修复以及疤痕愈合过程是非常重要的，这一发现可能有助于产生新的治疗炎症方法。

与炎症相关的拓展阅读：

• Nature：炎症性肠道疾病（IBD）的遗传研究
• Blood：抑制血栓及炎症发生的小分子物质多聚磷酸盐被发现
• eCAM：中和蛋白质HMGB1防止持久性炎症反应
• Rheumatology：急性痛风发作时SUA水平下降原因与全身炎症反应相关
• ARD：特发性炎症性肌病患者血清维生素D水平低 更多信息请点击：有关炎症更多资讯

Neutrophil-Delivered Myeloperoxidase Dampens the Hydrogen Peroxide Burst after Tissue Wounding in Zebrafish

Prompt neutrophil arrival is critical for host defense immediately after injury [1,2,3]. Following wounding, a hydrogen peroxide (H₂O₂) burst generated in injured tissues is the earliest known leukocyte chemoattractant [4]. Generating this tissue-scale H₂O₂ gradient uses dual oxidase [4] and neutrophils sense H₂O₂ by a mechanism involving the LYN Src-family kinase [5], but the molecular mechanisms responsible for H₂O₂ clearance are unknown [6]. Neutrophils carry abundant amounts of myeloperoxidase, an enzyme catalyzing an H₂O₂-consuming reaction [7,8]. We hypothesized that this neutrophil-delivered myeloperoxidase downregulates the high tissue H₂O₂ concentrations that follow wounding. This was tested in zebrafish using simultaneous fluorophore-based imaging of H₂O₂ concentrations and leukocytes [4,9,10,11] and a new neutrophil-replete but myeloperoxidase-deficient mutant (durif). Leukocyte-depleted zebrafish had an abnormally sustained wound H₂O₂ burst, indicating that leukocytes themselves were required for H₂O₂ downregulation. Myeloperoxidase-deficient zebrafish also had abnormally sustained high wound H₂O₂ concentrations despite similar numbers of arriving neutrophils. A local H₂O₂/myeloperoxidase interaction within wound-recruited neutrophils was demonstrated. These data demonstrate that leukocyte-delivered myeloperoxidase cell-autonomously downregulates tissue-generated wound H₂O₂ gradients in vivo, defining a new requirement for myeloperoxidase during inflammation. Durif provides a new animal model of myeloperoxidase deficiency closely phenocopying the prevalent human disorder [7,12,13], offering unique possibilities for investigating its clinical consequences.