Vesicle-associated membrane protein-8/endobrevin negatively regulates phagocytosis of bacteria in dendritic cells.

Phagocytosis is a specialized mechanism used by mammalian cells, particularly the cells of the immune system, such as dendritic cells (DC) and macrophages, to protect the host against infection. The process involves a complex cascade of pathways, from the ligation of surface receptors of phagocytes with components of the microorganism's surface, formation of phagosomes and subsequently phagolysosomes, to the eventual presentation of foreign Ags. Vesicle-associated membrane protein (VAMP)-8/endobrevin has been shown previously to function in the endocytic pathways. Our results showed that VAMP-8 colocalized with lysosome-associated membrane protein-2, and a significant amount of VAMP-8 was recruited to the phagosomes during bacterial ingestion. However, overexpression of VAMP-8 significantly inhibited phagocytosis in DC. We also found that the phagocytic activity of VAMP-8-/- DC was significantly higher than wild-type VAMP-8+/+ DC, thus further confirming that VAMP-8 negatively regulates phagocytosis in immature DC.