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

• Published in: Atherosclerosis 2011-04, Vol.215 (2), p.331-338
• Main Authors: Czepluch, Frauke S, Olieslagers, Servé, van Hulten, Ruud, Vöö, Stefan A, Waltenberger, Johannes
• Format: Article
• Language: English
• Subjects: Antioxidant enzyme; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; CD16; Cell Adhesion - physiology; Chemotaxis, Leukocyte - immunology; Drug toxicity and drugs side effects treatment; Humans; Lipopolysaccharide Receptors - immunology; Medical sciences; Migration; Monocyte; Monocytes - immunology; Monocytes - metabolism; Pharmacology. Drug treatments; PlGF-1; Reactive Oxygen Species - metabolism; Receptors, IgG - immunology; Toxicity: blood; Vascular Endothelial Growth Factor A - immunology; Vascular Endothelial Growth Factor Receptor-1 - biosynthesis; VEGF-A; VEGFR-1
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2011.01.004

Abstract 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.