生物谷：一组科学家最近发现，当在免疫细胞中得到表达时，一种负责调控血压的酶能防止肿瘤生长。研究结果发表在6月份的 American Journal of Pathology上。
血管紧缩素转化酶（ACE）直接起着控制血压的作用，并常用于治疗高血压。同时ACE还在如生育、免疫细胞发育、动脉硬化和产生有效的免疫反应等方面起着作用。为了证明ACE在癌症的免疫调制方面的作用，Emory大学的Kenneth Bernstein小组研究了只在巨噬细胞中表达ACE的老鼠（ACE 10/10）。
通过注射黑色素瘤细胞，正常老鼠发育出了大型的黑色素肿瘤，而ACE 10/10老鼠只发育出了很小的肿瘤。通过使用各种不同的黑色素瘤细胞和不同的表达高ACE水平的老鼠，科学家证明了ACE 10/10在对抗肿瘤中的作用。有趣的是，在ACE 10/10老鼠中白细胞水平很高，这表明存在大规模的抗癌免疫反应。
为了证明是否存在ACE引发的抗癌免疫反应，科学家取出了正常老鼠的骨髓，再注入ACE 10/10骨髓。当它们被注入黑色素瘤细胞后，表现出了控制肿瘤生长的能力。免疫反应还增加了T细胞数量，以及免疫活性化学物质的水平，并且降低了抑制免疫的物质。
这些研究表明，在巨噬细胞中高水平的ACE表达产生了强大的抗癌反应。除此之外，对于淋巴瘤细胞的类似研究也取得了同样效果，表明巨噬细胞ACE表达对于多种癌症都有重要意义。文章作者Shen表示：“这对于寻找治疗人类癌症的方法非常有用。” （援引教育部科技发展中心）
英文原文链接：http://www.physorg.com/news100270370.html
原始出处:
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.
