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CUTTING EDGE |
*
Department of Medicine, Division of Pulmonary and Critical Care, and the Will Rogers Institute Pulmonary Research Laboratory, University of California School of Medicine, Los Angeles, CA 90095; and
Department of Anatomy, Cell Biology, and Injury Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103
Recent reports highlighted the chemotactic activities of
antimicrobial peptide defensins whose structure, charge, and size
resemble chemokines. By assaying representative members of the four
known families of chemokines we explored the obverse: whether some
chemokines exert antimicrobial activity. In a radial diffusion assay,
only recombinant monokine induced by IFN-
(MIG/CXCL9),
IFN--inducible protein of 10 kDa (IP-10/CXCL10), and IFN-inducible T
cell 
chemoattractant (I-TAC/CXCL11), members of the
IFN--inducible tripeptide motif Glu-Leu-Arg (ELR)- CXC
chemokines, were antimicrobial against Escherichia coli
and Listeria monocytogenes. Similar to human defensins,
antimicrobial activities of the chemokines were inhibited by 50 and 100
mM NaCl. The concentration of MIG/CXCL9 and IP-10/CXCL10 released from
IFN--stimulated PBMC in 24 h were, respectively, 35- and
28-fold higher than from unstimulated cells. Additionally, the amounts
of chemokines released per monocyte suggest that, in tissues with
mononuclear cell infiltration, IFN--inducible chemokines may reach
concentrations necessary for microbicidal activity. IFN--inducible
chemokines may directly inactivate microbes before attracting other
host defense cells to the area of infection.
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D. Yang, Q. Chen, D. M. Hoover, P. Staley, K. D. Tucker, J. Lubkowski, and J. J. Oppenheim Many chemokines including CCL20/MIP-3{alpha} display antimicrobial activity J. Leukoc. Biol., September 1, 2003; 74(3): 448 - 455. [Abstract] [Full Text] [PDF]
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F. M. Assadi-Porter, F. Abildgaard, H. Blad, and J. L. Markley Correlation of the Sweetness of Variants of the Protein Brazzein with Patterns of Hydrogen Bonds Detected by NMR Spectroscopy J. Biol. Chem., August 15, 2003; 278(33): 31331 - 31339. [Abstract] [Full Text] [PDF]
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S. E. Blackwell and A. M. Krieg CpG-A-Induced Monocyte IFN-{gamma}-Inducible Protein-10 Production Is Regulated by Plasmacytoid Dendritic Cell-Derived IFN-{alpha} J. Immunol., April 15, 2003; 170(8): 4061 - 4068. [Abstract] [Full Text] [PDF]
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X. Zeng, T. A. Moore, M. W. Newstead, R. Hernandez-Alcoceba, W. C. Tsai, and T. J. Standiford Intrapulmonary Expression of Macrophage Inflammatory Protein 1{alpha} (CCL3) Induces Neutrophil and NK Cell Accumulation and Stimulates Innate Immunity in Murine Bacterial Pneumonia Infect. Immun., March 1, 2003; 71(3): 1306 - 1315. [Abstract] [Full Text] [PDF]
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M. Durr and A. Peschel Chemokines Meet Defensins: the Merging Concepts of Chemoattractants and Antimicrobial Peptides in Host Defense Infect. Immun., December 1, 2002; 70(12): 6515 - 6517. [Full Text] [PDF]
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Y.-Q. Tang, M. R. Yeaman, and M. E. Selsted Antimicrobial Peptides from Human Platelets Infect. Immun., December 1, 2002; 70(12): 6524 - 6533. [Abstract] [Full Text] [PDF]
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B. Mehrad, M. Wiekowski, B. E. Morrison, S.-C. Chen, E. C. Coronel, D. J. Manfra, and S. A. Lira Transient Lung-Specific Expression of the Chemokine KC Improves Outcome in Invasive Aspergillosis Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1263 - 1268. [Abstract] [Full Text] [PDF]
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D. M. Hoover, C. Boulegue, D. Yang, J. J. Oppenheim, K. Tucker, W. Lu, and J. Lubkowski The Structure of Human Macrophage Inflammatory Protein-3alpha /CCL20. LINKING ANTIMICROBIAL AND CC CHEMOKINE RECEPTOR-6-BINDING ACTIVITIES WITH HUMAN beta -DEFENSINS J. Biol. Chem., September 27, 2002; 277(40): 37647 - 37654. [Abstract] [Full Text] [PDF]
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K. Boztug, M. J. Carson, N. Pham-Mitchell, V. C. Asensio, J. DeMartino, and I. L. Campbell Leukocyte Infiltration, But Not Neurodegeneration, in the CNS of Transgenic Mice with Astrocyte Production of the CXC Chemokine Ligand 10 J. Immunol., August 1, 2002; 169(3): 1505 - 1515. [Abstract] [Full Text] [PDF]
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B. C. Schutte, J. P. Mitros, J. A. Bartlett, J. D. Walters, H. P. Jia, M. J. Welsh, T. L. Casavant, and P. B. McCray Jr. Discovery of five conserved beta -defensin gene clusters using a computational search strategy PNAS, February 19, 2002; 99(4): 2129 - 2133. [Abstract] [Full Text] [PDF]
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