Fractalkine Preferentially Mediates Arrest and Migration of CD16+ Monocytes

TLDR

CD16+ monocytes comprise 5–10 % of peripheral blood monocytes, expand markedly in sepsis, HIV‑1 infection, and cancer, secrete high levels of pro‑inflammatory cytokines, and their tissue recruitment mechanisms remain unknown. The study aims to elucidate the molecular mechanisms governing CD16+ monocyte trafficking, specifically whether distinct adhesion molecules and chemokine receptors mediate their migration. By comparing CD16+ and CD16− monocytes, the authors identified that migration is driven by different combinations of adhesion molecules and chemokine receptors. CD16+ monocytes express high CX3CR1 and CXCR4, low CCR2 and CD62L, migrate efficiently toward fractalkine and CXCL12 but not CCL2, arrest more frequently on FKN under flow, and thus fractalkine preferentially mediates their arrest and migration, implicating the CX3CR1‑FKN axis in vascular injury.

Abstract

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.