Function of the P2X7 receptor in hematopoiesis and leukemogenesis

Novel evidence that the P2X1 purinergic receptor–Nlrp3 inflammasome axis orchestrates optimal trafficking of hematopoietic stem progenitors cells

“…Mice deficient in expression of these receptors are poor mobilizers in response to G-CSF or AMD3100 and show defective homing and engraftment [2,3]. Based on our observations that HSPCs highly express P2X1 member of this receptor family and published data that it is highly sensitive to eATP [17][18][19] and plays a role in the migration of more differentiated hematopoietic and lymphopoietic cells [1,43] we become interested if this receptor similarly to P2X4 and P2X7 also affects migration of HSPCs. Herein, we confirmed the expression of this receptor by highly purified human and murine HSPCs and demonstrated by in vitro Transwell migration assays that this receptor is functional.…”

“…This latter chemoattractant as an extracellular mediator is mainly released from activated cells in a Pannexin-1 channel--dependent manner [10], acts in an autocrine/paracrine manner and activates P2X purinergic receptors [2,3]. These receptors are ligand-gated ion channels and consist of seven members P2X1-7 [1,7,12,13]. Our previous research demonstrated that two of these receptors, P2X4 and P2X7, are required for optimal trafficking of HSPCs [2,3].…”

“…P2X1 receptor has been described as highly expressed at smooth muscle cells and neurons [1,2]. For example, in response to eATP stimulation P2X1 mediates synaptic transmission between neurons and from neurons to smooth muscle and is responsible for sympathetic vasoconstriction in small arteries [2][3][4].…”

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

“…Since then, many papers have confirmed P2X7-dependent cancer-promoting activity and associated the expression of the receptor with increased cell metabolism, neo-vascularization, and, in general, poor patient prognoses [ 1 , 14 , 54 , 55 , 56 , 57 , 58 , 59 ]. Several solid and liquid cancer types overexpress P2X7, for which P2X7-targeting drugs are potential therapeutic tools; these include acute myeloid and chronic lymphocytic leukemia [ 9 , 42 , 60 , 61 , 62 , 63 ], melanoma [ 43 , 64 , 65 ], glioma [ 66 , 67 , 68 ], neuroblastoma [ 41 , 44 , 55 , 69 , 70 ] prostate, breast, bone, and colorectal cancer [ 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. As the above-cited literature demonstrate, P2X7 growth-promoting roles have been covered elsewhere; therefore, its extensive characterization is beyond the scope of the present overview.…”

Erythrocytes as Messengers for Information and Energy Exchange between Cells

“…Unlike other P2X receptors, the P2X7 receptor shows a rather extended C-terminal domain described as the "cytoplasmic ballast" [96]. The cytoplasmic ballast contains one GDP-binding site, two zinc-binding sites and similarity to TNF receptor I and lipopolysaccharide binding domains [97]. When exposed to high ATP concentrations, the P2X7 receptor can form a macropore that allows passage of solutes up to 900 Da in size leading to apoptosis of the cell.…”