ATP-induced activation of human B lymphocytes via P2-purinoceptors.
ATP-specific P2-purinoceptors expressed on various cell types have been shown to trigger cell activation via a phospholipase C pathway. In the present study, we provide evidence that P2-purinoceptors are expressed on B lymphocytes but not on T lymphocytes. ATP at concentrations of 10 to 100 microM triggered a dose-dependent increase in inositol 1,4,5-trisphosphate (IP3) levels as well as total inositol phosphate in human B lymphocytes. As expected from the changes in IP3, incubation of B cells with increasing concentrations of ATP lead to a dose-dependent increase in cytosolic free Ca+2 ([Ca+2]i). Extracellular ATP also induced increases in the levels of c-fos and c-myc mRNA. Because no responses were elicited by other nucleotides, the increase in IP3 production, the rise in [Ca+2]i levels, and the enhanced expression of c-fos and c-myc mRNA seem to be mediated by P2-purinoceptors. These responses were exclusive to B lymphocytes, in that ATP had no effect on IP3, [Ca+2]i, or oncogene expression in T cells. The results show that binding of extracellular ATP to P2-purinoceptors on quiescent B cells leads to the activation of genes associated with cell activation. This appears to be mediated via the phospholipase C signal transduction pathway.
Padeh
S
S
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Cohen
A
A
Roifman
C M
CM
D000251:Adenosine Triphosphatases / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011983:Receptors, Purinergic / Q000502:physiology*
D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011983:Receptors, Purinergic; C060980:phosphatidylinositol 3,4-diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D002118:Calcium