VEGF-A-induced chemotaxis of CD16+ monocytes is decreased secondary to lower VEGFR-1 expression.

BACKGROUND

Monocyte recruitment into the vessel wall is a crucial initial step in vascular repair, arteriogenesis and atherogenesis. Two distinct human monocyte subpopulations can be classified according to their CD14/16 surface expression, namely CD14++CD16-monocytes (CD16-mo) and CD14+CD16+ monocytes (CD16+mo). We investigated different functional properties of the two monocyte subsets.

METHODS

CD16-/CD16+mo were isolated from human blood by an immunological selection. We assessed monocyte chemokinesis, chemotaxis, adhesion and Vascular-Endothelial Growth Factor (VEGF) receptor expression. Furthermore, generation of reactive oxygen species (ROS) as well as expression of antioxidant enzymes was investigated.

RESULTS

Chemokinesis of CD16+mo was decreased compared to CD16-mo (p<0.01). Likewise, adhesion capacity of CD16+mo was weaker (p<0.05). CD16+mo chemotaxis towards the angiogenic ligands vascular endothelial growth factor-A (VEGF-A) and placenta growth factor-1 (PlGF-1) was reduced compared to CD16-mo. VEGFR-1 is the receptor for VEGF-A and PlGF-1 on monocytes. VEGFR-1 protein expression was lower in CD16+mo than in CD16-mo (p<0.05). The impaired VEGF-A- and PlGF-1-induced CD16+mo chemotaxis might therefore be attributed to the reduced VEGFR-1 expression. CD16+mo exhibited less spontaneous ROS production than CD16-mo. Additionally, the antioxidant enzyme manganese superoxide dismutase was expressed at higher levels in CD16+mo (p<0.05); this might partly explain the higher oxidative resistance of CD16+mo.

CONCLUSION

These novel functional differences between CD16-mo and CD16+mo may predict different functional roles of both monocyte subsets in vascular repair, arteriogenesis and atherogenesis.