The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth.
The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth.
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DOI：
10.4049/jimmunol.0902110
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Gallo RL
中科院分区：
文献类型：
--
作者：
Büchau AS;Morizane S;Trowbridge J;Schauber J;Kotol P;Bui JD;Gallo RL
肿瘤监测需要参与先天免疫和适应性免疫的多种分子和细胞的相互作用。Cathelicidin最初被鉴定为抗微生物肽，尽管现在很清楚它除了杀死微生物之外还具有多种免疫功能。最近的数据表明cathelicidin在肿瘤发展中的作用截然不同。由于其在肿瘤监测中的作用还不清楚，我们研究了cathelicidin在控制小鼠可移植肿瘤中的需求。在小鼠的肿瘤浸润性NK 1.1+细胞中观察到大量的Cathelicidin。在两种不同的异种移植肿瘤小鼠模型（B16.F10和RMA-S）中，凯萨林菌素敲除小鼠（Camp-/-）的肿瘤生长速度比野生型对照更快，这一事实证明了这一发现的重要性。体外功能分析发现，来自Camp−/−与野生型小鼠的NK细胞对肿瘤靶点的细胞毒性活性受损。这些发现不能完全归因于在新鲜分离的Camp−/− NK细胞中观察到的穿孔素缺乏，因为这种缺乏可以通过IL-2治疗部分恢复，而IL-2激活的Camp−/− NK细胞的细胞毒性活性仍然存在缺陷。因此，我们证明了一个以前未被认识到的作用，cathelicidin在NK细胞的抗肿瘤功能。
Tumor surveillance requires the interaction of multiple molecules and cells that participate in innate and the adaptive immunity. Cathelicidin was initially identified as an antimicrobial peptide, although it is now clear that it fulfills a variety of immune functions beyond microbial killing. Recent data have suggested contrasting roles for cathelicidin in tumor development. Because its role in tumor surveillance is not well understood, we investigated the requirement of cathelicidin in controlling transplantable tumors in mice. Cathelicidin was observed to be abundant in tumor-infiltrating NK1.1+ cells in mice. The importance of this finding was demonstrated by the fact that cathelicidin knockout mice (Camp−/−) permitted faster tumor growth than wild type controls in two different xenograft tumor mouse models (B16.F10 and RMA-S). Functional in vitro analyses found that NK cells derived from Camp−/− versus wild type mice showed impaired cytotoxic activity toward tumor targets. These findings could not be solely attributed to an observed perforin deficiency in freshly isolated Camp−/− NK cells, because this deficiency could be partially restored by IL-2 treatment, whereas cytotoxic activity was still defective in IL-2-activated Camp−/− NK cells. Thus, we demonstrate a previously unrecognized role of cathelicidin in NK cell antitumor function.
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