Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30839
Title: Modulation of P2X(7) purinergic receptor in macrophages by Leishmania amazonensis and its role in parasite elimination
Authors: Chaves, Suzana Passos
Santos, Eduardo Caio Torres
Marques, Camila
Figliuolo, Vanessa Ribeiro
Persechini, Pedro Muanis
Silva, Robson Coutinho
Bergmann, Bartira Rossi
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofisiologia. Laboratório de Imunobiofísica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofisiologia. Laboratório de Imunobiofísica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofisiologia. Laboratório de Imunobiofísica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofisiologia. Laboratório de Imunobiofísica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofisiologia. Laboratório de Imunobiofísica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Abstract: The purinergic P2X(7) receptor is a membrane protein of leucocytes involved in the clearance of intracellular bacteria such as Chlamydia and Mycobacterium. In this work, we investigated the role and modulation of macrophage P2X(7)R in intracellular infection with the protozoan parasite Leishmania amazonensis. Upon infection, isolated murine macrophages displayed enhanced expression of P2X(7)R and were significantly more responsive to extracellular ATP (ATPe)-induced pore opening, as demonstrated by the increased uptake of Lucifer Yellow. This was extended to the in vivo situation, where cells from established cutaneous lesions were more sensitive to ATPe than cells from uninfected mice. ATP treatment of infected macrophages inhibited parasite growth, and this was prevented by pre-treatment with oxidized ATP, a selective antagonist of P2X(7)R. Parasite killing was unlikely due to induction of nitric oxide production or cytolysis of infected macrophage, as those functions were unaltered with parasite-effective ATPe concentrations. A direct drug effect is also unlike, as ATPe enhanced axenic parasite growth. We found that leishmanial infection rendered wild-type but not P2X(7)R-deficient macrophages more prone to ATP-induced apoptosis. These results show that macrophage infection with L. amazonensis leads to enhanced expression of functional P2X(7)R, that upon ligation with ATPe helps in the elimination of the parasites by an as yet unclear mechanism possibly involving host cell apoptosis.
Keywords: ATP
Leishmania
Macrophage
Purinergic
Nucleotides
Apoptosis
keywords: Leishmania
Macrófagos
Purinérgicos
Nucleotídeos
Apoptose
Issue Date: 2009
Publisher: Elsevier
Citation: CHAVES, Suzana Passos; et al. Modulation of P2X7 purinergic receptor in macrophages by Leishmania amazonensis and its role in parasite elimination. Microbes and Infection, v.11, p.842-849, 2009.
DOI: 10.1016/j.micinf.2009.05.001
ISSN: 1286-4579
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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