title: Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.
abstract: Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Valdirene S
authors.initials: VS
authors.lastname: Muniz
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Baptista-Dos-Reis
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Benjamim
authors.affiliation: Pharmacy School, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Hilton A
authors.initials: HA
authors.lastname: Mata-Santos
authors.affiliation: Pharmacy School, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Alexandre S
authors.initials: AS
authors.lastname: Pyrrho
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Strauch
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Melo
authors.affiliation: Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Amanda R R
authors.initials: AR
authors.lastname: Vicentino
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Silva-Paiva
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Christianne
authors.initials: C
authors.lastname: Bandeira-Melo
authors.affiliation: Division of Infectious Diseases and Allergy and Inflammation, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Weller
authors.affiliation: Institute of Biomedical Sciences/Unit of Xerem, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Figueiredo
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Josiane S
authors.initials: JS
authors.lastname: Neves
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D018793:Interleukin-13 / Q000032:analysis / Q000097:blood; D015847:Interleukin-4 / Q000032:analysis / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018793:Interleukin-13; D058925:Receptors, Purinergic P2Y12; D015847:Interleukin-4; D000244:Adenosine Diphosphate; D003094:Collagen; D047209:Eosinophil Peroxidase