title: Human β defensin-3 induces chemokines from monocytes and macrophages: diminished activity in cells from HIV-infected persons.
abstract: Human β defensin-3 (hBD-3) is an antimicrobial peptide with diverse functionality. We investigated the capacity of hBD-3 and, for comparison, Pam3CSK4 and LL-37 to induce co-stimulatory molecules and chemokine expression in monocytes. These stimuli differentially induced CD80 and CD86 on the surface of monocytes and each stimulant induced a variety of chemokines including monocyte chemoattractant protein 1 (MCP-1), Gro-α, macrophage-derived chemokine (MDC) and macrophage inflammatory protein 1β (MIP1β), while only hBD-3 and Pam3CSK4 significantly induced the angiogenesis factor, vascular endothelial growth factor (VEGF). Human BD-3 induced similar chemokines in monocyte-derived macrophages and additionally induced expression of Regulated upon activation normal T-cell expressed and presumably secreted (RANTES) in these cells. Comparison of monocytes from HIV(+) and HIV(-) donors indicated that monocytes from HIV(+) donors were more likely to spontaneously express certain chemokines (MIP-1α, MIP-1β and MCP-1) and less able to increase expression of other molecules in response to hBD-3 (MDC, Gro-α and VEGF). Chemokine receptor expression (CCR5, CCR2 and CXCR2) was relatively normal in monocytes from HIV(+) donors compared with cells from HIV(-) donors with the exception of diminished expression of the receptor for MDC, CCR4, which was reduced in the patrolling monocyte subset (CD14(+)  CD16(++) ) of HIV(+) donors. These observations implicate chemokine induction by hBD-3 as a potentially important mechanism for orchestrating cell migration into inflamed tissues. Alterations in chemokine production or their receptors in monocytes of HIV-infected persons could influence cell migration and modify the effects of hBD-3 at sites of inflammation.
authors.affiliation: Department of Biological Sciences, Case School of Dental Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Velizar
authors.initials: V
authors.lastname: Petrov
authors.forename: Nicholas
authors.initials: N
authors.lastname: Funderburg
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.forename: Scott
authors.initials: S
authors.lastname: Sieg
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018836:Inflammation Mediators / Q000378:metabolism*; D055666:Lipopeptides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D019707:Receptors, Chemokine / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D018925:Chemokines; C422950:DEFB103A protein, human; D018836:Inflammation Mediators; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D019707:Receptors, Chemokine; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D023083:beta-Defensins; D054804:Cathelicidins
keywords: HIV; chemokine; defensin; macrophage; monocyte