DEFENSINS - A FAMILY OF ANTIMICROBIAL AND CYTOTOXIC PEPTIDES
DEFENSINS - A FAMILY OF ANTIMICROBIAL AND CYTOTOXIC PEPTIDES
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DOI：
10.1016/0300-483x(94)90158-9
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发表时间：
1994-02-28
期刊：
影响因子：
4.5
通讯作者：
LEHRER, RI
中科院分区：
文献类型：
--
作者：
KAGAN, BL;GANZ, T;LEHRER, RI
防御素是抗菌和细胞毒性肽，含有 29-35 个氨基酸残基，包括 6 个形成 3 个分子内二硫键的不变半胱氨酸。它们占人和兔中性粒细胞 (PMN) 总细胞蛋白的 5% 以上，也由兔肺巨噬细胞以及鼠和人小肠潘氏细胞产生。防御素在体外对许多革兰氏阳性和革兰氏阴性细菌、真菌、分枝杆菌和一些包膜病毒发挥抗菌作用，并对多种正常和恶性靶标具有细胞毒性，包括对 TNF-α 和 NK 细胞溶解因子耐药的细胞。当对侧施加大约 70-90 mV 的负电压时，人和兔子的防御素在各种平面脂质双层中形成电压敏感通道。这些通道显示出适度的阴离子选择性，并且它们的形成受到防御素浓度的强烈影响。尽管大多数其他通道形成肽具有显着的 α 螺旋结构域，但防御素分子的结构主要由反平行 β 折叠组成。对各种原核和真核细胞的研究提供了令人信服的证据，表明防御素通过在易感细胞膜上形成电压调节通道来杀死这些靶标。防御素敏感靶标的广谱性以及血液、肺和肠道的专门宿主防御细胞中防御素的丰度表明，防御素可能在针对感染和肿瘤的先天免疫中发挥重要作用。
Defensins are antimicrobial and cytotoxic peptides that contain 29-35 amino acid residues, including 6 invariant cysteines that form 3 intramolecular disulfide bonds. They constitute more than 5% of the total cellular protein of human and rabbit neutrophils (PMN), and are also produced by rabbit lung macrophages and by murine and human small intestinal Paneth cells. Defensins exerted antimicrobial effects in vitro against many Gram-positive and Gram-negative bacteria, fungi, mycobacteria and some enveloped viruses, and were cytotoxic to a wide range of normal and malignant targets, including cells resistant to TNF-alpha and NK-cytolytic factor. Human and rabbit defensins formed voltage-sensitive channels in a variety of planar lipid bilayers when a negative voltage of approximately 70-90 mV was applied to the contralateral side. These channels showed modest anion selectivity and their formation was strongly influenced by defensin concentration. Although most other channel-forming peptides have prominent alpha-helical domains, the structure of defensin molecules is primarily composed of antiparallel beta-sheets. Studies with various prokaryotic and eukaryotic cells provided convincing evidence that defensins killed these targets by forming voltage-regulated channels in the susceptible cell's membrane. The broad spectrum of defensin-susceptible targets and the abundance of defensins in specialized host defense cells of the blood, lungs and intestinal tract suggest that defensins could play a significant role in innate immunity to infection and neoplasia.