Signal transduction and white cell maturation via extracellular ATP and the P2Y(11) receptor

Extracellular ATP promotes a wide range of physiological effects in many ti ssues. Of particular interest is the effect of ATP on leukaemia-derived HL- 60 and NB4 cell lines, which are induced to mature to neutrophil-like cells . The differentiation process appears to be mediated by ATP binding to a ce ll-surface purinergic P2Y receptor, resulting in the stimulation of adenyly l cyclase, elevation of cAMP levels and activation of protein kinase A. In 1997, a novel ATP-selective P2Y receptor, P2Y(11), was cloned and shown to be linked to both cAMP and Ca2+ signalling pathways. The pharmacological pr ofile of ATP analogues used by P2Y(11) for cAMP production in transfected c ells is reviewed in the present paper and shown to be closely similar to th e profiles for cAMP production and differentiation of myeloblastic HL-60 ce lls and promyelocytic NB4 cells, both of which express P2Y(11). Additional data are provided showing that HL-60 mature to neutrophil-like cells in res ponse to extracellular ATP, as measured by upregulation of the N-formyl pep tide receptor, N-formyl peptide-mediated actin polymerization and superoxid e production. It is proposed that P2Y(11) is responsible for the ATP-mediat ed differentiation of these cells lines and that this receptor may play a r ole in the maturation of granulocytic progenitors in the bone marrow.