FIG. 4.

Critical roles of extracellular ATP on immune responses. (A) Extracellular ATP has diverse effects on various immune cells, such as macrophages, neutrophils, or T cells. The functional roles of ATP are mediated by P2XR or P2YR. ATP activates NLRP3 inflammasome and promotes secretion of IL-1β and IL-18 in macrophages primed with TLR ligands. ATP also promotes migration and transmigration of immune cells to inflamed sites, killing bacteria, and chemotaxis. The roles of ATP on DCs include maturation and migration of DC and cytokine production. (B) ATP-mediated P2XR or P2YR activation leads to various cellular events. Upon activation of P2XR and P2YR by ATP, potassium efflux and calcium mobilization rapidly occur, which induce activation of NLRP3 inflammasome or MAPKs, leading to initiation of proinflammatory cascade. ATP treatment also causes NADPH oxidase-dependent ROS generation and promotes fusion of phagosome and lysosome, resulting in promoting bacterial killing. DC, dendritic cell; MAPK, mitogen-activated protein kinase; NADPH, nicotinamide adenine dinucleotide phosphate; ROS, reactive oxygen species. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars