Vascular Endothelial Growth Factor Inhibits Phagocytosis of Apoptotic Cells by Airway Epithelial Cells

Abstract

Professional phagocytes such as dendritic cells and macrophages can ingest particles larger than 0.5 μm in diameter. Epithelial cells are nonprofessional phagocytes that cannot ingest pathogenic microorganisms, but they can ingest apoptotic cells. Inhibition of the engulfment of apoptotic cells by the airway epithelium can cause severe airway inflammation. Vascular endothelial growth factor (VEGF) is an angiogenesis-promoting factor that can mediate allergic airway inflammation and can promote airway epithelial cells (AECs) proliferation, but it is not clear whether it affects the engulfment of apoptotic cells by AECs. In the present study, VEGF inhibited engulfment of apoptotic cells by AECs via binding to VEGF receptor(R)2. This inhibitory effect of VEGF was not influenced by masking of phosphatidylserine (PS) on the surface of apoptotic cells and was partially mediated by the PI3K-Akt signaling pathway. VEGF inhibition of phagocytosis involved polymerization of actin and downregulation of the expression of the phagocytic-associated protein Beclin-1 in AECs. Since engulfment of apoptotic cells by AECs is an important mechanism for airway inflammation regression, VEGF inhibition of the engulfment of apoptotic cells by airway epithelial cells may be important for mediating allergic airway inflammation.