title: Periodate-oxidized ATP modulates macrophage functions during infection with Leishmania amazonensis.
abstract: Previously, we showed that treating macrophages with ATP impairs the intracellular growth of Leishmania amazonensis, and that the P2X7 purinergic receptor is overexpressed during leishmaniasis. In the present study, we directly evaluated the effect of periodate-oxidized ATP (oATP) on parasite control in Leishmania-infected macrophages. We found that oATP impaired the attachment/entrance of L. amazonensis promastigotes to C57BL/6 mouse macrophages in a P2X7 receptor-independent manner, as macrophages from P2X7(-/-) mice were similarly affected. Although oATP directly inhibited the growth of axenic promastigotes in culture, promoted rapid ultrastructural alterations, and impaired Leishmania internalization by macrophages, it did not affect intracellular parasite multiplication. Upon infection, phagosomal acidification was diminished in oATP-treated macrophages, accompanied by reduced endosomal proteolysis. Likewise, MHC class II molecules expression and ectoATPase activity was decreased by oATP added to macrophages at the time of parasite infection. These inhibitory effects were not due to a cytotoxic effect, as no additional release of lactate dehydrogenase was detected in culture supernatants. Moreover, the capacity of macrophages to produce nitric oxide and reactive oxygen species was not affected by the presence of oATP during infection. We conclude that oATP directly affects extracellular parasite integrity and macrophage functioning.
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho-IBCCF, Universidade Federal do Rio de Janeiro, RJ, Brazil; Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Brasil.
authors.forename: V R
authors.initials: VR
authors.lastname: Figliuolo
authors.forename: S P
authors.initials: SP
authors.lastname: Chaves
authors.forename: G F
authors.initials: GF
authors.lastname: Santoro
authors.forename: C M L M
authors.initials: CM
authors.lastname: Coutinho
authors.forename: J R
authors.initials: JR
authors.lastname: Meyer-Fernandes
authors.forename: B
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.forename: R
authors.initials: R
authors.lastname: Coutinho-Silva
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007891:Leishmania / Q000276:immunology; D007896:Leishmaniasis / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*
chemical_list: D000949:Histocompatibility Antigens Class II; D017382:Reactive Oxygen Species; D058486:Receptors, Purinergic P2X7; C004282:periodate-oxidized adenosine 5'-triphosphate; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase
keywords: Leishmania amazonensis; acidification; oxidized adenosine triphosphate; phagosomal maturation