一条小斑马鱼的尾部在被割破后3分钟、17分钟和61分钟（由上至下）的图像，从中可以看到，过氧化氢从伤口释放，并随着向组织的扩散而不断褪色。（图片提供:Philipp Niethammer）

任何曾在擦破的膝盖上感受到过氧化氢“冒泡”的刺痛的家伙都会对这种化合物的消毒本领念念不忘。然而美国科学家的最新研究表明，过氧化氢的功能远非杀死微生物般简单——它还有“要求增援”，召唤抗菌细胞大军赶赴伤口的功效。
 
被刺破的皮肤会引发一个有关化学信号的连锁反应，即激活血液凝结，以及吸引一批免疫细胞来防御微生物的入侵。其中的一些细胞（例如白血球）通过发起一种“呼吸暴发”——能够释放高活性杀菌分子，包括由身体自身产生的过氧化氢——来杀死入侵者。
 
美国波士顿市哈佛医学院的博士后、生物学家Philipp Niethammer在注意到一些奇怪的现象后，决定尝试在斑马鱼受伤的尾部诱发一次过氧化氢的爆发。Niethammer说：“我在伤口发现了某些物质的暴发，但我在这里却没有找到白血球。”实验显示，这种暴发的物质是过氧化氢——它比白血球的出现平均早了17分钟，而人们通常认为，过氧化氢正是由白血球所形成的。就Niethammer看来，这似乎更像是在说白血球是被过氧化氢带到伤口来的，而非是由白血球释放了过氧化氢。
 
为了证明这一假设，Niethammer和他的同事用一种已知能够抑制过氧化氢形成的化合物处理了斑马鱼的幼体。当研究人员在抑制剂存在的环境下将小鱼的尾部割破后，白血球竟然迟迟不来：与正常状态下的4条到6条鱼相比，平均只有不到1条鱼的伤口能够在42分钟内出现白血球。接下来，研究人员利用遗传手段确定了与过氧化氢形成有关的酶——这种名为duox的蛋白质也同时存在于人体的甲状腺、消化道和肺脏之中。这些组织的额外炎症会导致哮喘和其他疾病，因此duox可能在这些疾病的发病过程中扮演了一个重要角色。研究人员在6月4日出版的《自然》杂志上报告了这一研究成果。
 
英国布里斯托尔大学的细胞生物学家Paul Martin认为，这项研究工作找到了伤口愈合的一个关键时间节点。他说：“现在我们知道了第一个步骤。”那么，这种装在棕色药瓶中的过氧化物真的能够将白血球带到伤口来吗？Niethammer说，这是一个尚未解决的问题。他目前正在研究究竟是白血球直接发现了过氧化氢，还是这种化合物仅仅是一个更长的信号链中的一部分。

推荐原始出处：

Nature advance online publication 3 June 2009 | doi:10.1038/nature08119

A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish

Philipp Niethammer1,4, Clemens Grabher2,4,5, A. Thomas Look2,3 & Timothy J. Mitchison1

1 Department of Systems Biology, Harvard Medical School, Boston,
2 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
3 Division of Hematology/Oncology, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
4 These authors contributed equally to this work.
5 Present address: Karlsruhe Institute of Technology, Forschungszentrum Karlsruhe GmbH, Institute of Toxicology and Genetics, 76344 Eggenstein-Leopoldshafen, Germany.

Barrier structures (for example, epithelia around tissues and plasma membranes around cells) are required for internal homeostasis and protection from pathogens. Wound detection and healing represent a dormant morphogenetic program that can be rapidly executed to restore barrier integrity and tissue homeostasis. In animals, initial steps include recruitment of leukocytes to the site of injury across distances of hundreds of micrometres within minutes of wounding. The spatial signals that direct this immediate tissue response are unknown. Owing to their fast diffusion and versatile biological activities, reactive oxygen species, including hydrogen peroxide (H2O2), are interesting candidates for wound-to-leukocyte signalling. Here we probe the role of H2O2 during the early events of wound responses in zebrafish larvae expressing a genetically encoded H2O2 sensor1. This reporter revealed a sustained rise in H2O2 concentration at the wound margin, starting 3 min after wounding and peaking at 20 min, which extended 100–200 m into the tail-fin epithelium as a decreasing concentration gradient. Using pharmacological and genetic inhibition, we show that this gradient is created by dual oxidase (Duox), and that it is required for rapid recruitment of leukocytes to the wound. This is the first observation, to our knowledge, of a tissue-scale H2O2 pattern, and the first evidence that H2O2 signals to leukocytes in tissues, in addition to its known antiseptic role.