Published online before print June 16, 2003
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display antimicrobial activity
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*Basic Research Program and Macromolecular Crystallography and Opportunistic Infection Laboratories, Division of Cancer Treatment and Diagnosis/Developmental Therapeutics Program, Science Applications International Corp., Inc.-Frederick, and Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Maryland
@ To whom correspondence should be addressed. E-mail: oppenhei{at}mail.ncifcrf.gov.
Previous studies have demonstrated that 
-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3
(MIP-3). Structural analysis of CCL20/MIP-3 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-3 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.
Key Words: defensin • macrophage-inflammatory protein • colony-forming assay
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