Yang De, Chen Qian, Hoover David M, Staley Patricia, Tucker Kenneth D, Lubkowski Jacek, Oppenheim Joost J
Division of Cancer Treatment and Diagnosis, Science Applications International Corp., Inc.-Frederick, Maryland 21702, USA.
J Leukoc Biol. 2003 Sep;74(3):448-55. doi: 10.1189/jlb.0103024.
Previous studies have demonstrated that beta-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3alpha (MIP-3alpha). Structural analysis of CCL20/MIP-3alpha revealed that most of the positively charged residues are concentrated at one area of its topological surface, a characteristic considered to be important for the antimicrobial activity of defensins. Here, we report that similar to defensins, CCL20/MIP-3alpha has antimicrobial effects on Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus, and Candida albicans. Additionally, by screening a total of 30 human chemokines, we have identified an additional 17 human chemokines, which exhibit antimicrobial activity in vitro. Collectively, about two-thirds of the chemokines investigated so far has the capacity to kill microorganisms in vitro, suggesting that antimicrobial activity may be another host-defense function for certain chemokines. Comparison of the structural characteristics between antimicrobial and nonantimicrobial chemokines suggests that topological formation of a large, positively charged electrostatic patch on the surface of the molecule is likely to be a common structural feature of antimicrobial chemokines.
先前的研究表明，β-防御素通过与CC趋化因子配体CCL20/巨噬细胞炎性蛋白-3α（MIP-3α）共享趋化因子受体CCR6来展现趋化活性。CCL20/MIP-3α的结构分析显示，大多数带正电荷的残基集中在其拓扑表面的一个区域，这一特征被认为对防御素的抗菌活性很重要。在此，我们报告，与防御素类似，CCL20/MIP-3α对大肠杆菌、铜绿假单胞菌、卡他莫拉菌、化脓性链球菌、粪肠球菌、金黄色葡萄球菌和白色念珠菌具有抗菌作用。此外，通过对总共30种人类趋化因子进行筛选，我们又鉴定出17种在体外具有抗菌活性的人类趋化因子。总体而言，目前所研究的趋化因子中约三分之二具有在体外杀死微生物的能力，这表明抗菌活性可能是某些趋化因子的另一种宿主防御功能。对抗菌趋化因子和非抗菌趋化因子的结构特征进行比较表明，分子表面形成一个大的、带正电荷的静电斑的拓扑结构可能是抗菌趋化因子的一个共同结构特征。
