Cutting edge: IFN-inducible ELR- CXC chemokines display defensin-like antimicrobial activity.
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-gamma (MIG/CXCL9), IFN-gamma-inducible protein of 10 kDa (IP-10/CXCL10), and IFN-inducible T cell alpha chemoattractant (I-TAC/CXCL11), members of the IFN-gamma-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-gamma-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-gamma-inducible chemokines may reach concentrations necessary for microbicidal activity. IFN-gamma-inducible chemokines may directly inactivate microbes before attracting other host defense cells to the area of infection.
Cole
A M
AM
Department of Medicine, Division of Pulmonary and Critical Care, University of California School of Medicine, Los Angeles, CA 90095, USA. acole@mednet.ucla.edu
Ganz
T
T
Liese
A M
AM
Burdick
M D
MD
Liu
L
L
Strieter
R M
RM
D020816:Amino Acid Motifs; D000900:Anti-Bacterial Agents / Q000276:immunology*; D001120:Arginine / Q000378:metabolism; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology*; D017124:Conserved Sequence; D023082:Defensins / Q000096:biosynthesis / Q000276:immunology*; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000276:immunology*
D000900:Anti-Bacterial Agents; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D023082:Defensins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D018698:Glutamic Acid; D007371:Interferon-gamma; D001120:Arginine; D007930:Leucine