TLR4激活的血小板附著到嗜中性粒細(xì)胞上從而導(dǎo)致嗜中性粒細(xì)胞胞外殺菌網(wǎng)絡(luò)(neutrophil extracellular traps, NETs)形成,，圖片來(lái)自Nature Medicine, 2007 Apr; 13(4):463-9,，在此引用僅作研究之用,，版權(quán)歸Kubes P.所有,。
英國(guó)伯明翰大學(xué)科學(xué)家發(fā)現(xiàn)一種方法來(lái)觸發(fā)體內(nèi)被稱(chēng)作嗜中性粒細(xì)胞的保護(hù)性白細(xì)胞產(chǎn)生一種強(qiáng)有力的抗細(xì)菌感染DNA“蜘蛛”網(wǎng)。
伯明翰大學(xué)牙醫(yī)學(xué)院研究人員使用次氯酸(Hypochlorous acid, HOCl)讓病人嗜中性粒細(xì)胞產(chǎn)生這種被稱(chēng)作嗜中性粒細(xì)胞胞外殺菌網(wǎng)絡(luò)(neutrophil extracellular traps, NETs)的“蜘蛛”網(wǎng),，其中這些病人患有一種特殊疾病即慢性肉芽腫病(chronic granulomatous disease, CGD)而使得他們的嗜中性粒細(xì)胞在自然條件下不能夠產(chǎn)生這種胞外殺菌網(wǎng)絡(luò),。相關(guān)研究結(jié)果發(fā)表在2012年2月那期Clinical and Experimental Immunology期刊上,。
最近研究已經(jīng)表明當(dāng)嗜中性粒細(xì)胞---形成體內(nèi)抵抗細(xì)菌感染的第一道防御線的白細(xì)胞---遭受著細(xì)菌的大量攻擊時(shí),，這些細(xì)胞以一種特異性控制的方式開(kāi)始死亡。作為最后一搏,，它們釋放來(lái)自自身細(xì)胞核內(nèi)的全部DNA到周?chē)M織,。正是這種DNA形成粘性的“蜘蛛”網(wǎng)，而且這種網(wǎng)一旦捕捉住細(xì)菌,，就利用它含有的酶來(lái)破壞它們,。
伯明翰大學(xué)牙周研究小組教授Iain Chapple和博士Paul Cooper領(lǐng)導(dǎo)的一個(gè)科學(xué)家研究團(tuán)隊(duì)發(fā)現(xiàn)次氯酸刺激CGD病人產(chǎn)生嗜中性粒細(xì)胞胞外殺菌網(wǎng)絡(luò)。他們也發(fā)現(xiàn)“?；撬?taurine)”降低這種胞外殺菌網(wǎng)絡(luò)形成,，因而可能延長(zhǎng)嗜中性粒細(xì)胞存活。
Chapple教授評(píng)論道：“我們對(duì)這種胞外殺菌網(wǎng)絡(luò)在抵抗導(dǎo)致牙周病(periodontal disease)發(fā)生的細(xì)菌過(guò)程中所起的作用感到興趣,，不過(guò)關(guān)于胞外殺菌網(wǎng)絡(luò)形成的基礎(chǔ)生物學(xué)特征對(duì)很多傳染性免疫疾病而言是共同的,。”
“我們知道這種胞外殺菌網(wǎng)絡(luò)形成需要氧自由基，但是CGD病人的嗜中性粒細(xì)胞不能有效地產(chǎn)生氧自由基,，因而不能夠產(chǎn)生該胞外殺菌網(wǎng)絡(luò),，或者說(shuō)不能對(duì)某些感染作出反應(yīng)。這項(xiàng)研究有助于我們更多一點(diǎn)理解這些過(guò)程,，而且可能在未來(lái)導(dǎo)致人們開(kāi)發(fā)出新的治療策略來(lái)增加或者在某些情形下降低這種胞外殺菌網(wǎng)絡(luò)形成,。”
不過(guò)研究人員也特別強(qiáng)調(diào)關(guān)于嗜中性粒細(xì)胞胞外殺菌網(wǎng)絡(luò)的多種矛盾之處。“在一些病人當(dāng)中,，這種胞外殺菌網(wǎng)絡(luò)似乎在殺死細(xì)菌中起著非常重要的作用”,，Professor Chapple報(bào)道，“但是在其他一些病人當(dāng)中,，他們似乎產(chǎn)生自身抗體對(duì)抗該胞外殺菌網(wǎng)絡(luò)中的組分,，從而與某些免疫介導(dǎo)的疾病如類(lèi)風(fēng)濕性關(guān)節(jié)炎和自身免疫血管炎相關(guān)聯(lián)在一起。因此,，對(duì)一些病人而言,，這種胞外殺菌網(wǎng)絡(luò)可能是一把雙刃劍，不過(guò)當(dāng)前關(guān)于這個(gè)免疫控制新領(lǐng)域的研究正在如火如荼地開(kāi)展,，因而激動(dòng)人心的發(fā)現(xiàn)將在接下來(lái)的5到10年內(nèi)紛沓而來(lái),。” (生物谷：towersimper編譯)
doi:10.1111/j.1365-2249.2011.04518.x
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Hypochlorous acid regulates neutrophil extracellular trap release in humans
L. J. Palmer, P. R. Cooper, M. R. Ling, H. J. Wright, A. Huissoon, I. L. C. Chapple
Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine.
