Finally, MCP-1-induced chemotaxis was inhibited at all concentrations of the drug, with a slight dose-dependent effect (P < 0·05 for all) (Table 1). When MDC chemotaxis was tested, MVC in vitro treatment induced a significant reduction of cell migration towards RANTES, MIP-1β, fMLP and MCP-1. RANTES-induced chemotaxis was decreased significantly by 0·1 µM, 1 µM and 10 µM

of MVC (69% ± 6, 68% ± 6 and 72% ± 5 of the control, respectively; P < 0·05 for all concentrations) (Fig. 1a). MIP-1β-induced chemotaxis of MDC was of 57% (±9), 54% (±9) Ipilimumab in vitro and 45% (±12) of the control after treatment with 0·1 µM, 1 µM and 10 µM of MVC, respectively (P < 0·001 for all three concentrations) (Fig. 1b). MVC inhibited fMLP-induced chemotaxis of MDC in a dose-dependent manner (53% ± 28, 37% ± 19 and 33% ± 17 of the control after treatment with 0·1 µM, 1 µM and 10 µM of MVC, respectively (P < 0·001 for all three concentrations) (Fig. 1c). Finally, MCP-1-induced chemotaxis selleck of MDC was of 50% (±8), 66% (±11) and 43% (±10) of the control after treatment with 0·1 µM, 1 µM and 10 µM of MVC, respectively (P < 0·005 for all) (Fig. 1d). A representative experiment of MDC chemotactic activity measured by Boyden's chamber

method and Diff-Quik staining of filters is illustrated in Fig. 2. In another set of experiments, cell viability and phenotype (CD14 for monocytes, MO and CD1a for MDC) and expression of chemoattractant receptors CCR1, CCR4, CCR5 and FPR expression were investigated. We found no alteration in viability and phenotype in cells treated with MVC (data not shown). Moreover, treatment with different concentrations of MVC did not modulate CCR1, CCR4, CCR5 and FPR expression in monocytes, MO and MDC. The median of MFI in six independent experiments is reported in Table 2. Recent lines of evidence suggest that MVC, the first CCR5 antagonist approved

in clinical practice for treatment of HIV infection, exhibit additional immunological effects beyond the pure anti-HIV inhibitory activity [10,11]. Given the central role of CCR5 in inflammation and cellular recruitment at the site of infection, analysis of the effect of CCR5 antagonists on cell migration may represent an area of active investigation [12]. In a recent paper, ID-8 we demonstrated that PBMCs from HIV-infected patients exhibited diminished migratory responses toward fMLP after initiation of an anti-retroviral regimen containing MVC [13]. In order to investigate if this phenomenon could be related to a direct effect of the drug, we analysed cell chemotactic activity after in vitro treatment with MVC. We found that MVC exhibited the ability to inhibit the chemotactic activity of PBMCs in response to fMLP and to CCR5-binding chemokine RANTES. In the present study, we have investigated further the in vitro immunological effect of MVC by assessing the migratory capacity of APC, including monocytes, MO and MDC.