生物谷：一組科學(xué)家最近發(fā)現(xiàn),，當(dāng)在免疫細(xì)胞中得到表達(dá)時，一種負(fù)責(zé)調(diào)控血壓的酶能防止腫瘤生長,。研究結(jié)果發(fā)表在6月份的 American Journal of Pathology上,。
血管緊縮素轉(zhuǎn)化酶（ACE）直接起著控制血壓的作用，并常用于治療高血壓,。同時ACE還在如生育,、免疫細(xì)胞發(fā)育、動脈硬化和產(chǎn)生有效的免疫反應(yīng)等方面起著作用,。為了證明ACE在癌癥的免疫調(diào)制方面的作用,，Emory大學(xué)的Kenneth Bernstein小組研究了只在巨噬細(xì)胞中表達(dá)ACE的老鼠（ACE 10/10）。
通過注射黑色素瘤細(xì)胞,，正常老鼠發(fā)育出了大型的黑色素腫瘤,，而ACE 10/10老鼠只發(fā)育出了很小的腫瘤,。通過使用各種不同的黑色素瘤細(xì)胞和不同的表達(dá)高ACE水平的老鼠，科學(xué)家證明了ACE 10/10在對抗腫瘤中的作用,。有趣的是,，在ACE 10/10老鼠中白細(xì)胞水平很高，這表明存在大規(guī)模的抗癌免疫反應(yīng),。
為了證明是否存在ACE引發(fā)的抗癌免疫反應(yīng),，科學(xué)家取出了正常老鼠的骨髓,，再注入ACE 10/10骨髓,。當(dāng)它們被注入黑色素瘤細(xì)胞后，表現(xiàn)出了控制腫瘤生長的能力,。免疫反應(yīng)還增加了T細(xì)胞數(shù)量,，以及免疫活性化學(xué)物質(zhì)的水平，并且降低了抑制免疫的物質(zhì),。
這些研究表明,，在巨噬細(xì)胞中高水平的ACE表達(dá)產(chǎn)生了強(qiáng)大的抗癌反應(yīng)。除此之外,，對于淋巴瘤細(xì)胞的類似研究也取得了同樣效果,，表明巨噬細(xì)胞ACE表達(dá)對于多種癌癥都有重要意義。文章作者Shen表示：“這對于尋找治療人類癌癥的方法非常有用,。” （援引教育部科技發(fā)展中心）
英文原文鏈接：http://www.physorg.com/news100270370.html
原始出處:
American Journal of Pathology. 2007;170:2122-2134
DOI: 10.2353/ajpath.2007.061205
Mice with Enhanced Macrophage Angiotensin-Converting Enzyme Are Resistant to Melanoma
Xiao Z. Shen*, Ping Li*, Daiana Weiss, Sebastien Fuchs*, Hong D. Xiao*, Jon A. Adams*, Ifor R. Williams*, Mario R. Capecchi, W. Robert Taylor and Kenneth E. Bernstein*
From the Department of Pathology and Laboratory Medicine,* Emory University, Atlanta, Georgia; the Department of Medicine, Emory University, Atlanta, Georgia; and the Howard Hughes Medical Institute, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah
Angiotensin-converting enzyme (ACE) is a peptidase responsible for the cleavage of angiotensin I and several other peptides. Here, gene targeting was used to switch control of the ACE locus from the endogenous promoter to the macrophage-specific c-fms promoter. Challenge of these mice, called ACE 10/10, with the aggressive mouse melanoma cell line B16 showed that they are remarkably resistant to tumor growth. Tumor resistance was seen after challenge with different melanoma cell lines and in mice with different genetic backgrounds. Histological study of the tumors that did grow in ACE 10/10 mice showed an enhanced inflammatory response. ACE 10/10 mice had increased numbers of tumor epitope-specific CD8+ T cells after challenge with melanoma or lymphoma. ACE 10/10 macrophages showed increased production of interleukin-12 and nitric oxide but reduced interleukin-10. Engraftment of wild-type mice with ACE 10/10 bone marrow transferred B16 tumor resistance. Injection of B16 tumors with ACE 10/10 macrophages also reduced tumor growth. ACE 10/10 mice may define a new means of enhancing the immune response, which may be potentially useful in several human clinical situations.
