Fig. 5.

Schematic representation of the modulation of CD39 activity through P2X7 receptor signaling in activated macrophages. Under homeostatic conditions (upper panel) TLR2, the P2X7 receptor and CD39 are present in several lipid raft microdomains on the cell surface, while TLR4 is located outside the rafts. In contrast, during inflammation (lower panel) (1) the recognition of PAMPs – such as bacterial lipopolysaccharide (LPS) – by PRRs can induces ATP release, thereby activating the P2X7 receptor. This, in turn, induces (2) an extensive release of ATP that occurs via the P2X7 receptor itself or via pannexin hemichannels, thereby increasing caveolin-1 expression and the formation of caveolar domains on the plasma membrane. (3) In these domains, CD39 might become more stable and active, favoring the process of ATP hydrolysis to ADP and its metabolites, which, in a purinergic regulatory mechanism, could contribute to limit macrophage activation and inflammation.