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 transendo-thelial migration in response to fractalkine (FKN; FKN/CX3CL1) and stromal-derived factor 1α (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.