P2 receptors-mediated responses in human eosinophils.

Although it is increasing appreciated that P2 receptors play a pivotal role in macrophage and dendritic cell functions, little is known about expression and function of P2 receptors in human eosinophils (1, 2). We have investigated expression and function of P2 receptors expressed in these cells, with the following results: A) Human eosinophils express mRNA for the following P2 receptor subtypes: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, and P2X1, P2X4, P2X7. B) Stimulation with extracellular nucleotides results in: a) Intracellular Ca2+ increases. b) Actin polymerization. c) Production of large amounts of reactive oxygen intermediates. These events were inhibited by P2 receptors antagonists. d) CD11b-expression. e) Chemotaxis. Although all tested nucleotides (ATP, ATPgammaS, alpha,beta-meATP, 2-MeSATP, BzATP, ADP, CTP and UTP) are able to induce all the reported responses, agonists that preferentially activate G protein-coupled P2Y receptors (2-MeSATP, UTP and ADP) are more potent than the P2X agonists alpha,beta-meATP and BzATP in inducing the production of reactive oxygen metabolites, actin polymerization and chemotaxis. On the contrary, both P2Y and P2X agonists show similar potency in inducing intracellular calcium transients and CD11b up-regulation. These conclusions are further supported by experiments with pertussis toxin, KN-62 or by experiments performed in Ca2+-free conditions, indicating participation of different P2 receptor subtypes in the regulation of eosinophils responses (3, 4). Bibliography: 1) Saito et al., 1991. Int Arch Allergy Appl Immunol 94:68-70. 2) Mohanty et al., 2001. J Allergy Clin Immunol 107:849-855. 3) Ferrari et al., 2000. FEBS Lett 486:217-224. 4) Idzko et al., 2001. J Cell Physiol 188:329-336