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 1alpha (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.