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Many chemokines including CCL20/MIP-3 alpha display antimicrobial activity

  1. Author:
    Yang, D.
    Chen, Q.
    Hoover, D. M.
    Staley, P.
    Tucker, K. D.
    Lubkowski, J.
    Oppenheim, J. J.

  2. Author Address

    NCI, LMI, CCR, Bldg 560,Room 21-89, Frederick, MD 21702 USA NCI, LMI, CCR, Frederick, MD 21702 USA Sci Applicat Int Corp Inc, Basic Res Program, Frederick, MD USA Sci Applicat Int Corp Inc, Macromol Crystallog Labs, Frederick, MD USA Sci Applicat Int Corp Inc, Opportunist Infect Labs, Div Canc Treatment, Frederick, MD USA Sci Applicat Int Corp Inc, Diag Dev Therapeut Program, Frederick, MD USA Oppenheim JJ NCI, LMI, CCR, Bldg 560,Room 21-89, Frederick, MD 21702 USA
    1. Year: 2003
  2. Journal: Journal of Leukocyte Biology
    1. 74
    2. 3
    3. Pages: 448-455
  4. Type of Article: Article
  1. Abstract:

    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 CCL20/3HP- 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.

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