CCR2 blockade of monocyte migration is less potent at higher CD11b integrin levels in HIV-1 infection (P6213)

Abstract

Abstract Monocytes are a key contributor to HIV inflammation and HIV-associated neurocognitive disorders by migrating into the brain in response to chemokine gradients, such as MCP-1 (a CCR2 ligand). We sought to characterize the migration capacity of monocytes from HIV infected adults. Cryopreserved peripheral blood mononuclear cells from HIV-1 infected adults (n=6) were incubated with BMS-22 (blocks MCP-1 binding to CCR2) and transferred to a transwell migration system, and put under an MCP-1 gradient. Migrated cells were collected and stained for CD3, CD14, CD16, HLA-DR, CCR2, CCR5 and CD11b. Cells were acquired on a Fortessa flow cytometer and analyzed using FlowJo. MCP-1 caused a significant increase in migration compared to baseline (3.0 fold change, p = 0.01) in the absence of BMS-22. There was a significant inverse correlation between CD11b mean fluorescence intensity (MFI) and degree of inhibition of migration by BMS-22 (rho = -0.88, p = 0.03). A trend between higher CCR2 and CCR5 MFI and lower migratory rates was also observed. Higher CD11b rates associated with poorer inhibition of migration by BMS-22, a CCR2 but not CD11b antagonist. Blocking MCP-1 is being pursued as a novel treatment method in HIV. The incomplete inhibition of monocyte migration at higher CD11b expression levels by a CCR2 antagonist highlights compensatory mechanisms between CCR2 and integrins, and indicates CD11b levels could guide effective use of CCR2 antagonist based therapies in humans.