一條小斑馬魚的尾部在被割破后3分鐘、17分鐘和61分鐘（由上至下）的圖像,，從中可以看到，過氧化氫從傷口釋放，并隨著向組織的擴散而不斷褪色,。（圖片提供:Philipp Niethammer）
任何曾在擦破的膝蓋上感受到過氧化氫“冒泡”的刺痛的家伙都會對這種化合物的消毒本領(lǐng)念念不忘。然而美國科學(xué)家的最新研究表明,，過氧化氫的功能遠非殺死微生物般簡單——它還有“要求增援”,，召喚抗菌細胞大軍趕赴傷口的功效。
被刺破的皮膚會引發(fā)一個有關(guān)化學(xué)信號的連鎖反應(yīng),，即激活血液凝結(jié),，以及吸引一批免疫細胞來防御微生物的入侵。其中的一些細胞（例如白血球）通過發(fā)起一種“呼吸暴發(fā)”——能夠釋放高活性殺菌分子，包括由身體自身產(chǎn)生的過氧化氫——來殺死入侵者,。
美國波士頓市哈佛醫(yī)學(xué)院的博士后,、生物學(xué)家Philipp Niethammer在注意到一些奇怪的現(xiàn)象后，決定嘗試在斑馬魚受傷的尾部誘發(fā)一次過氧化氫的爆發(fā),。Niethammer說：“我在傷口發(fā)現(xiàn)了某些物質(zhì)的暴發(fā),，但我在這里卻沒有找到白血球。”實驗顯示,，這種暴發(fā)的物質(zhì)是過氧化氫——它比白血球的出現(xiàn)平均早了17分鐘,，而人們通常認為，過氧化氫正是由白血球所形成的,。就Niethammer看來,，這似乎更像是在說白血球是被過氧化氫帶到傷口來的，而非是由白血球釋放了過氧化氫,。
為了證明這一假設(shè),，Niethammer和他的同事用一種已知能夠抑制過氧化氫形成的化合物處理了斑馬魚的幼體。當研究人員在抑制劑存在的環(huán)境下將小魚的尾部割破后,，白血球竟然遲遲不來：與正常狀態(tài)下的4條到6條魚相比,，平均只有不到1條魚的傷口能夠在42分鐘內(nèi)出現(xiàn)白血球。接下來,，研究人員利用遺傳手段確定了與過氧化氫形成有關(guān)的酶——這種名為duox的蛋白質(zhì)也同時存在于人體的甲狀腺,、消化道和肺臟之中。這些組織的額外炎癥會導(dǎo)致哮喘和其他疾病,，因此duox可能在這些疾病的發(fā)病過程中扮演了一個重要角色,。研究人員在6月4日出版的《自然》雜志上報告了這一研究成果。
英國布里斯托爾大學(xué)的細胞生物學(xué)家Paul Martin認為,，這項研究工作找到了傷口愈合的一個關(guān)鍵時間節(jié)點,。他說：“現(xiàn)在我們知道了第一個步驟。”那么,，這種裝在棕色藥瓶中的過氧化物真的能夠?qū)籽驇У絺趤韱?？Niethammer說，這是一個尚未解決的問題,。他目前正在研究究竟是白血球直接發(fā)現(xiàn)了過氧化氫,，還是這種化合物僅僅是一個更長的信號鏈中的一部分。
生物谷推薦原始出處：
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.
