Figure 1.

Putative role of purinergic signaling in driving macrophages and T cell activation in atheroma development. DAMPs (LDL, oxLDL, extracellular ATP) and PAMPs (viruses, microbes, LPS) trigger the production of cytokines and oxygen species by monocytes (1). This induces release of ATP from the endothelial cells and expression of the leukocyte adhesion molecules (vascular cell adhesion molecule 1, VCAM-1; intercellular adhesion molecule 1, ICAM-1) (2) thus prompting adhesion and extravasation of monocytes and lymphocytes (3). Macrophage derived ROS oxidate LDL to oxLDL (4) and stimulate IL-1β and IL-18 production (5). Extracellular ATP is also converted to ADO by CD39 and CD73, which are expressed by the intima cells (6). ADO exerts a down-modulation of the immune response therefore has a protective effect. On the contrary, ATP acts as a proinflammatory molecule inducing the cleavage of CD62L by ADAM17 and T cell polarization to a Th1 phenotype (7). Upon engulfment of oxLDL, macrophages become foam cells (8). The atheroma “necrotic core” (right part of the figure) forms by accumulation of dying foam cells, lipids, cholesterol crystals and immune cells (9). Pro-inflammatory IFN-γ and TNF-α are released upon antigen presentation to T lymphocytes by DC (10), and in turn promote IL-8 and VEGF secretion, with consequent fibroblasts and SMC migration and proliferation (11).