ATP secreted by endothelial cells blocks CX3CL1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y11 receptor activation

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

“…NK cells NK cells are reported to express P2X1, P2X4-7, and all P2Y receptor subtypes on m RNA level [183]. Schmidt et al were the first to study the functional effect of ATP on NK cells showing that the treatment of human NK cells with ATP resulted in a strong inhibition of their cytotoxic activity on K562 target cells [184], a result that was corroborated by others [185,186].…”

“…Consequently, activated Treg cells are able to abrogate the P2X7-mediated suppression of Treg function and stability in an autologous way [169]. c Natural killer (NK) cells: NK cells stimulated with ATP increases chemokinesis and chemotaxis to CXCL12 via P2Y 11 receptor activation, while chemotaxis and NK cellmediated killing in response to CX3CL1 chemokine is inhibited [183]. APC antigen presenting cell, CX3CL1 chemokine (C-X3-C motif) ligand 1, CX3CR1 CX3C chemokine receptor 1, CXCL12 chemokine (C-X-C motif) ligand 12, CXCR4 C-X-C chemokine receptor type 4, DAMP damage-associated molecular patterns, Foxp3 forkhead box P3, HMC class II major histocompatibility complex class II, IL-6R interleukin-6 receptor, PAMP pathogen-associated molecular patterns, RORC retinoic acid receptor-related orphan receptor C. Values between brackets in figure represent reference numbers [168].…”

“…Miller et al equally confirmed that ATP and related adenine nucleotides play a role in decreased NK cell activity [187] but in contrast to the previous studies, the authors reported that this was in fact due to an inhibition of proliferation because despite a reduced thymidine incorporation induced by extracellular adenine nucleotides, NK cells maintained their capacity to lyse K562 cells in their experiments [187]. Extracellular ATP furthermore regulates NK cell cytotoxicity via P2Y 11 receptor activation; NK cells stimulated with ATP increased chemokinesis and inhibited NK chemotaxis in response to CX3CL1 chemokine [183].…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…A high-cholesterol diet decreased the spontaneous and NA-evoked release of ATP from caudal artery of aged rats, leading to an increase in blood pressure, and it was suggested that the main source of ATP was the endothelial cells, with a lesser contribution of smooth muscle (Hashimoto et al, 1998b). On the other hand, ATP release from endothelial cells by shear stress is enhanced in inflammatory states (Bodin and Purinergic Signaling and Blood Vessels , and this might represent a protective mechanism by inhibiting natural killer (NK) cell recruitment and consequently NK cell-mediated plaque formation, a mechanism suggested to involve P2Y 11 receptors (Gorini et al, 2010). NK cells represent the main source of interferon-g that contributes to atherosclerotic plaque progression; fractalkine expressed by endothelial cells mediates NK recruitment, and its killing of endothelial cells and high fractalkine mRNA is found in advanced atherosclerotic lesions in human arteries.…”

A critical look at the function of the P2Y11 receptor

“…Several of these studies report P2Y 11 activation in various immune cells to result in a pro-inflammatory response. The effects include a lower rate of CX 3 CL-mediated endothelial killing and migration in natural killer (NK) cells [123], delayed apoptosis in neutrophils [124], and increased chemotaxis in granulocytes [58,59]. In mesenchymal stem cells, NAD + stimulation of P2Y 11 resulted in cytokine release and chemotaxis [60].…”