title: Role of P2 Receptors as Modulators of Rat Eosinophil Recruitment in Allergic Inflammation.
abstract: ATP and other nucleotides are released from cells through regulated pathways or following the loss of plasma membrane integrity. Once outside the cell, these compounds can activate P2 receptors: P2X ionotropic receptors and G protein-coupled P2Y receptors. Eosinophils represent major effector cells in the allergic inflammatory response and they are, in fact, associated with several physiological and pathological processes. Here we investigate the expression of P2 receptors and roles of those receptors in murine eosinophils. In this context, our first step was to investigate the expression and functionality of the P2X receptors by patch clamping, our results showed a potency ranking order of ATP>ATPγS> 2meSATP> ADP> αβmeATP> βγmeATP>BzATP> UTP> UDP>cAMP. This data suggest the presence of P2X1, P2X2 and P2X7. Next we evaluate by microfluorimetry the expression of P2Y receptors, our results based in the ranking order of potency (UTP>ATPγS> ATP > UDP> ADP >2meSATP > αβmeATP) suggests the presence of P2Y2, P2Y4, P2Y6 and P2Y11. Moreover, we confirmed our findings by immunofluorescence assays. We also did chemotaxis assays to verify whether nucleotides could induce migration. After 1 or 2 hours of incubation, ATP increased migration of eosinophils, as well as ATPγS, a less hydrolysable analogue of ATP, while suramin a P2 blocker abolished migration. In keeping with this idea, we tested whether these receptors are implicated in the migration of eosinophils to an inflammation site in vivo, using a model of rat allergic pleurisy. In fact, migration of eosinophils has increased when ATP or ATPγS were applied in the pleural cavity, and once more suramin blocked this effect. We have demonstrated that rat eosinophils express P2X and P2Y receptors. In addition, the activation of P2 receptors can increase migration of eosinophils in vitro and in vivo, an effect blocked by suramin.
authors.affiliation: Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Anael Viana Pinto
authors.initials: AV
authors.lastname: Alberto
authors.affiliation: Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Robson Xavier
authors.initials: RX
authors.lastname: Faria
authors.affiliation: Laboratório de Neuroanatomia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Joao Ricardo Lacerda
authors.initials: JR
authors.lastname: de Menezes
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Surrage
authors.affiliation: Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Natasha Cristina
authors.initials: NC
authors.lastname: da Rocha
authors.affiliation: Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Leonardo Gomes Braga
authors.initials: LG
authors.lastname: Ferreira
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Valber da Silva
authors.initials: Vda S
authors.lastname: Frutuoso
authors.affiliation: Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Luiz Anastácio
authors.initials: LA
authors.lastname: Alves
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007477:Ions / Q000378:metabolism; D008297:Male; D009711:Nucleotides / Q000378:metabolism; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*
chemical_list: D007477:Ions; D009711:Nucleotides; D018048:Receptors, Purinergic P2; D002118:Calcium