Human hemoglobin-derived peptides exhibit antimicrobial activity:: a class of host defense peptides
Human hemoglobin-derived peptides exhibit antimicrobial activity:: a class of host defense peptides
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DOI：
10.1016/s1570-0232(03)00245-9
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发表时间：
2003-07-05
影响因子：
3
通讯作者：
Forssmann, WG
中科院分区：
文献类型：
--
作者：
Liepke, C;Baxmann, S;Forssmann, WG
血红蛋白是具有多种功能的生物活性肽的已知来源。在本研究中，我们首次报道了天然加工血红蛋白片段在人体中表现出抗菌活性的存在。从人胎盘肽库中纯化了两种抗菌血红蛋白来源的肽，通过连续色谱步骤跟踪对大肠杆菌BL21的最大生长抑制活性。这些肽由17个和36个氨基酸残基组成，分别被鉴定为γ -血红蛋白和β -血红蛋白的c端片段。抗菌β -血红蛋白片段也从裂解的红细胞中纯化出来，这表明血红蛋白的蛋白水解降解已经开始在红细胞内形成小的生物活性肽。鉴定的多肽在微摩尔浓度下抑制革兰氏阳性和革兰氏阴性细菌和酵母的生长。此外，通过脂多糖结合，β -血红蛋白片段降低内毒素的生物活性。相反，即使在高浓度下，所鉴定的抗菌血红蛋白肽对人原代血细胞也没有毒性活性。我们得出结论，抗菌血红蛋白衍生肽可能是先天免疫反应杀死微生物的重要效应器。入侵者。(C) 2003 Elsevier Science B.V.版权所有
Hemoglobin is a known source of biologically active peptides with various functions. In the present study, we report for the first time the existence of natural processed hemoglobin fragments exhibiting antimicrobial activity in humans. Two antimicrobial hemoglobin-derived peptides were purified from a human placental peptide library by consecutive chromatographic steps tracking the maximum growth inhibitory activity against Escherichia coli BL21. These peptides, consisting of 17 and 36 amino acid residues, were identified as being C-terminal fragments of gamma-hemoglobin and beta-hemoglobin, respectively. The antimicrobial beta-hemoglobin fragment was also purified from lysed erythrocytes, demonstrating that proteolytic degradation of hemoglobin into small bioactive peptides already starts inside erythrocytes. The identified peptides inhibit the growth of Gram-positive and Gram-negative bacteria and yeasts in micromolar concentrations. Moreover, by LPS-binding, the beta-hemoglobin fragment reduces biological activity of endotoxins. In contrast, even at high concentrations, the identified antimicrobial hemoglobin peptides do not exhibit toxic activity on human primary blood cells. We conclude that antimicrobial hemoglobin-derived peptides could be important effectors of the innate immune response killing microbial. invaders. (C) 2003 Elsevier Science B.V. All rights reserved.