生物谷報道：最近美國愛荷華大學(xué)的一項研究揭示了一種新的存在于正常氣管中的免疫防御機制,，這項研究能更好地解釋為什么囊性纖維化患者更易于罹患肺部細菌性感染。這項研究結(jié)果也為尋求這種疾病的新療法指明了道路,。
愛荷華大學(xué)的研究揭示了氣管宿主防御系統(tǒng)是抵御細菌侵襲最有效的防御系統(tǒng)之一,，正常氣管中能產(chǎn)生兩種酶并利用反應(yīng)性氧分子（ROS）殺傷細菌,。同時他們發(fā)現(xiàn)在囊性纖維化基因突變的氣管組織和細胞中此過程缺陷，囊性纖維化患者先天性免疫能力弱的一個可能原因是缺乏這種天然的宿主氧化防御機制,。
他們?nèi)〔拇笫?、奶牛和人類的氣管細胞及組織，發(fā)現(xiàn)了兩種酶,，一種是氣管酶（Duox）,能產(chǎn)生過氧化氫,，第二種酶是乳酸過氧化物酶 （lactoperoxidase)，可利用過氧化氫將一種稱為硫氰酸的小分子轉(zhuǎn)變?yōu)榭梢詺⑺兰毦膆ypothiocyanite。他們同時發(fā)現(xiàn),，CF基因發(fā)生突變的患者無法將關(guān)鍵分子硫氰酸運輸穿越氣管細胞,，因此不能生成具有殺傷作用的hypothiocyanite。換言之,，硫氰酸分子的缺乏打破了氧化抗菌系統(tǒng),。
硫氰酸一般存在于體液中，如血液和唾液,。除名稱和化學(xué)結(jié)構(gòu)上和氰化物有相似之處外,，硫化氫是無毒的。Hypothiocyanite對人體細胞和組織同樣是無害的,，但它能非常有效地殺傷細菌,，包括那些與囊性纖維化患者肺部致命感染密切普遍相關(guān)的菌種—金黃色葡萄菌和綠膿桿菌。如果能使硫氰酸在氣管表面粘液層中維持一定的濃度,，或許可以嘗試使用噴霧的方法,，輔助增強囊性纖維化患者的宿主防御系統(tǒng)，避免致命性肺部細菌感染,。”
此項研究是由囊性纖維化基金會部分資助,。研究結(jié)果發(fā)表在11月2日美國呼吸和急癥醫(yī)學(xué)雜志的網(wǎng)絡(luò)版中。
原文出處：
University of Iowa News Release
Nov. 30, 2006
Newly Discovered Immune Defense May Be Impaired In CF Airways
A recent University of Iowa study reveals a new immune defense mechanism in normal airways and may help explain why people with cystic fibrosis (CF) are particularly susceptible to bacterial lung infections. The findings also may point the way to new approaches for treating the disease.
The UI study shows how two enzymes generate and use reactive oxygen species (ROS) to destroy bacteria in normal airways. The team also found that this process is defective in airway tissue and cells containing the CF gene mutation. The study is published in the Nov. 2 online issue of the American Journal of Respiratory and Critical Care Medicine.
"Among the host defense systems that we know of in the airway, at least in cell culture and tissue explants, this is one of the most efficient antibacterial system we have identified," said Botond Banfi, M.D., Ph.D., UI assistant professor of anatomy and cell biology and senior study author. "The findings suggest that one reason for CF patients' weakened innate immunity might be the absence of this natural oxidative host defense mechanism."
Banfi added that correcting the problem by reconstituting the oxidative system might represent a totally new approach for preventing the onset of bacterial lung infections that often become chronic and eventually fatal in CF patients.
Working with airway cells and tissues from rats, cows and humans, the UI team uncovered the oxidative system, which produces hypothiocyanite -- a highly effective antibacterial compound. Banfi and his colleagues, including Patryk Moskwa, M.D., Ph.D., a UI postdoctoral fellow and first author of the study, showed that one airway enzyme (Duox) makes hydrogen peroxide and a second enzyme (lactoperoxidase) uses the hydrogen peroxide to convert a small molecule called thiocyanate into the bacteria-killing hypothiocyanite.
The UI researchers also showed that the critical thiocyanate cannot be transported across airway cells with the CF mutation, which means that hypothiocyanite is not produced. In other words, without thiocyanate the oxidative antibacterial system breaks down.
These results suggest that thiocyanate may not be present in the airway surface liquid of individuals with CF. Banfi and his colleagues intend to test that hypothesis by comparing thiocyanate levels in airway surface liquid from CF patients and from healthy individuals.
Thiocyanate is naturally present in body fluids like blood and saliva. Despite its name and its chemical relationship to cyanide, thiocyanate is not toxic. Hypothiocyanite is also harmless to human cells and tissues, but the UI team found that it is extremely efficient at killing bacteria including those most commonly associated with fatal lung infections in CF patients - Staphylococcus aureus and Pseudomonas aeruginosa.
"If we could reconstitute thiocyanate concentrations in the airway surface liquid, perhaps using a nebulizer, it might boost host defenses in CF patients and help prevent bacterial lung infections," Banfi said.
In addition to Banfi and Moskwa, the UI team included graduate student, Daniel Lorentzen; Katherine Excoffon, Ph.D., associate research scientist; Joseph Zabner, M.D., professor of internal medicine; Paul McCray, M.D., the Roy J. Carver Chair in Pulmonary Research and professor of pediatrics; and William Nauseef, M.D., professor of internal medicine. Corinne Dupuy at INSERM in Paris, France also was part of the research team.
The study was funded in part by the Cystic Fibrosis Foundation.
STORY SOURCE: University of Iowa Health Science Relations, 5135 Westlawn, Iowa City, Iowa 52242-1178
PHOTO: A photo of Dr. Banfi is available online at http://www.anatomy.uiowa.edu/pages/directory/faculty/bonfi.htm
CONTACT: Jennifer Brown, 319-335-9917 [email protected]
http://news-releases.uiowa.edu/2006/november/113006immune-defense.html
