ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells
| Autor: | Silvia Bulfone-Paus, Zane Orinska, Friedrich Haag, Vadim Budagian, Elena Bulanova, Friedrich Koch-Nolte |
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| Rok vydání: | 2009 |
| Předmět: |
Chemokine
Cell Membrane Permeability medicine.medical_treatment Immunology Apoptosis Biology chemistry.chemical_compound Mice Adenosine Triphosphate Extracellular medicine Immunology and Allergy Animals Mast Cells Receptor Cells Cultured Mice Knockout Mitogen-Activated Protein Kinase 3 Receptors Purinergic P2 Purinergic receptor Degranulation Tyrosine phosphorylation Cell Biology Cell biology Cytokine chemistry Receptors Purinergic P2X biology.protein Cytokines Receptors Purinergic P2X7 Chemokines Receptors Purinergic P2X3 |
| Zdroj: | Journal of leukocyte biology. 85(4) |
| ISSN: | 1938-3673 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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