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.