Fractalkine preferentially mediates arrest and migration of CD16+ monocytes.
CD16+ monocytes represent 5-10% of peripheral blood monocytes in normal individuals and are dramatically expanded in several pathological conditions including sepsis, human immunodeficiency virus 1 infection, and cancer. CD16+ monocytes produce high levels of proinflammatory cytokines and may represent dendritic cell precursors in vivo. The mechanisms that mediate the recruitment of CD16+ monocytes into tissues remain unknown. Here we investigate molecular mechanisms of CD16+ monocyte trafficking and show that migration of CD16+ and CD16- monocytes is mediated by distinct combinations of adhesion molecules and chemokine receptors. In contrast to CD16- monocytes, CD16+ monocytes expressed high CX3CR1 and CXCR4 but low CCR2 and CD62L levels and underwent efficient transendothelial migration in response to fractalkine (FKN; FKN/CX3CL1) and stromal-derived factor 1 alpha (CXCL12) but not monocyte chemoattractant protein 1 (CCL2). CD16+ monocytes arrested on cell surface-expressed FKN under flow with higher frequency compared with CD16- monocytes. These results demonstrate that FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions.
Ancuta
Petronela
P
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Rao
Ravi
R
Moses
Ashlee
A
Mehle
Andrew
A
Shaw
Sunil K
SK
Luscinskas
F William
FW
Gabuzda
Dana
D
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002453:Cell Cycle / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016131:Lymphocyte Subsets; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D017452:Receptors, IgG