title: Anti-infective peptide IDR-1002 augments monocyte chemotaxis towards CCR5 chemokines.
abstract: Innate defense regulator (IDR) peptides are a class of immunomodulators which enhance and modulate host innate immune responses against microbial pathogens. While IDR-mediated protection against a range of bacterial pathogens is dependent on enhanced monocyte recruitment to the site of infection, the mechanisms through which they increase monocyte trafficking remain unclear. In this study, anti-infective peptide IDR-1002 was shown to enhance monocyte chemotaxis towards chemokines CCL3 and CCL5. This enhancement correlated with the selective upregulation of CCR5 surface expression by peptide-treated monocytes. It was found that IDR-1002 enhancement of monocyte chemotaxis was fully dependent on CCR5 function. Furthermore, IDR-1002 enhanced chemokine-induced monocyte p38 MAPK phosphorylation in a CCR5-dependent fashion. Overall, these results indicate that peptide IDR-1002 can selectively influence monocyte recruitment by host chemokines through the regulation of chemokine receptors.
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, V6T 1Z4, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Madera
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, V6T 1Z4, Canada. Electronic address: bob@hancocklab.com.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000276:immunology; D018946:Chemokine CCL5 / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D019713:Receptors, CCR5 / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; C515429:CCL3 protein, human; C483024:CCL5 protein, human; C584933:CCR5 protein, human; D054405:Chemokine CCL3; D018946:Chemokine CCL5; C549067:IDR 1002; D007155:Immunologic Factors; D019713:Receptors, CCR5; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Chemokine receptors; Chemokines; Immunomodulation; Innate defense regulators; Monocytes