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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0808470

Received for publication July 31, 2008.
Revised December 8, 2008.
Accepted for publication December 24, 2008.

Article

ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells

Elena Bulanova *@, Vadim Budagian *, Zane Orinska *, Friedrich Koch-Nolte {dagger}, Friedrich Haag {dagger}, and Silvia Bulfone-Paus *

*Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany; and {dagger}Institute of Immunology, Hamburg University Medical Center Eppendorf, Hamburg, Germany

@ To whom correspondence should be addressed. E-mail: ebulanova{at}fz-borstel.de.


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Abstract

Extracellul ar 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, ligand-gated ion channel, 7 (P2X7) receptor-mediated membrane permeabilization, apoptosis, and cytokine expression in murine mast cells (MCs). Here, we report that MCs deficient in the expression of the P2X7 receptor are resistant to the ATP-induced membrane permeabilization and apoptosis. However, ATP affects the tyrosine phosphorylation pattern of P2X7 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, P2X1 and P2X3. 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.

Key Words: apoptosis • cell permeabilization • degranulation