CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells.
The CD16+ subset of peripheral blood monocytes (Mo) is expanded dramatically during inflammatory conditions including sepsis, HIV-1 infection, and cancer. CD16+ express high levels of CX3CR1, which mediates arrest onto CX3CL1-expressing endothelial cells (EC) under flow conditions. In contrast, attachment of CD16- Mo onto cytokine-activated EC is independent of CX3CL1. Here, we investigate the ability of CD16+ and CD16- Mo to produce proinflammatory cytokines upon interaction with CX3CL1-expressing HUVEC. We demonstrate that CD16+ but not CD16- Mo produce high levels of IL-6, CCL2, and matrix metalloproteinase (MMP)-9 when cocultured with TNF/IFN-gamma-activated HUVEC or nonactivated HUVEC expressing CX3CL1. Furthermore, supernatants from Mo cocultured with cytokine-activated HUVEC induce neuronal death in vitro. These results suggest that membrane-bound CX3CL1 stimulates production of IL-6, CCL2, and MMP-9 by CD16+ Mo, likely via engagement of CX3CR1. Thus, expansion of CD16+ Mo and their accumulation onto CX3CL1-expressing EC may result in recruitment of Mo and T cell subsets at sites of inflammation in response to CCL2, IL-6-induced cell activation and/or differentiation, and MMP-9-mediated vascular and tissue injury.
Ancuta
Petronela
P
Department of Cancer Immunology, and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Wang
Jianbin
J
Gabuzda
Dana
D
D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000276:immunology; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000096:biosynthesis* / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology
C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D015850:Interleukin-6; D008565:Membrane Proteins; D017452:Receptors, IgG; D020780:Matrix Metalloproteinase 9