ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells.
Extracellular ATP mediates a diverse array of biological responses in many cell types and tissues, including immune cells. We have demonstrated that ATP induces purinergic receptor P2X(7) mediated membrane permeabilization, apoptosis, and cytokine expression in murine mast cells (MCs). Here, we report that MCs deficient in the expression of the P2X(7) receptor are resistant to the ATP-induced membrane permeabilization and apoptosis. However, ATP affects the tyrosine phosphorylation pattern of P2X(7)knockout cells, leading to the activation of ERK1/2. Furthermore, ATP induces expression of several cytokines and chemokines in these cells, including IL-4, IL-6, IFN-gamma, TNF-alpha, RANTES, and MIP-2, at the mRNA level. In addition, the release of IL-6 and IL-13 to cell-conditioned medium was confirmed by ELISA. The ligand selectivity and pharmacological profile indicate the involvement of two P2X family receptors, P2X(1) and P2X(3). Thus, depending on genetic background, particular tissue microenvironment, and ATP concentration, MCs can presumably engage different P2X receptor subtypes, which may result in functionally distinct biological responses to extracellular nucleotides. This finding highlights a novel level of complexity in the sophisticated biology of MCs and may facilitate the development of new therapeutic approaches to modulate MC activities.
Bulanova
Elena
E
Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany. ebulanova@fz-borstel.de
Budagian
Vadim
V
Orinska
Zane
Z
Koch-Nolte
Friedrich
F
Haag
Friedrich
F
Bulfone-Paus
Silvia
S
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism* / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D058486:Receptors, Purinergic P2X7
D018925:Chemokines; D016207:Cytokines; C546409:P2rx3 protein, mouse; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D048052:Mitogen-Activated Protein Kinase 3