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Periodate‐oxidized ATP modulates macrophage functions during infection with Leishmania amazonensis

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 contro...

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Published in:Cytometry. Part A 2014-07, Vol.85 (7), p.588-600
Main Authors: Figliuolo, V. R., Chaves, S. P., Santoro, G. F., Coutinho, C. M. L. M., Meyer‐Fernandes, J. R., Rossi‐Bergmann, B., Coutinho‐Silva, R.
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creator Figliuolo, V. R.
Chaves, S. P.
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Coutinho‐Silva, R.
description 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. © 2014 International Society for Advancement of Cytometry
doi_str_mv 10.1002/cyto.a.22449
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subjects acidification
Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - pharmacology
Animals
Bone Marrow Cells - cytology
Bone Marrow Cells - immunology
Bone Marrow Cells - parasitology
Histocompatibility Antigens Class II - biosynthesis
L-Lactate Dehydrogenase - secretion
Leishmania - immunology
Leishmania amazonensis
Leishmaniasis - drug therapy
Leishmaniasis - immunology
Leishmaniasis - parasitology
Macrophages - immunology
Macrophages - parasitology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide - biosynthesis
oxidized adenosine triphosphate
phagosomal maturation
Reactive Oxygen Species - metabolism
Receptors, Purinergic P2X7 - genetics
title Periodate‐oxidized ATP modulates macrophage functions during infection with Leishmania amazonensis
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