title: Infection with Leishmania amazonensis upregulates purinergic receptor expression and induces host-cell susceptibility to UTP-mediated apoptosis.
abstract: Nucleotides are released into the extracellular milieu from infected cells and cells at inflammatory sites. The extracellular nucleotides bind to specific purinergic (P2) receptors and thereby induce a variety of cellular responses including anti-parasitic effects. Here we investigated whether extracellular nucleotides affect leishmanial infection in macrophages, and found that UTP reduces strongly the parasite load in peritoneal macrophages. Ultrastructural analysis of infected cells revealed that UTP induced morphological damage in the intracellular parasites. Uridine nucleotides also induced dose-dependent apoptosis of macrophages and production of ROI and RNI only in infected macrophages. The intracellular calcium measurements of infected cells showed that the response to UTP, but not UDP, increased the sensitivity and amplitude of cytosolic Ca(2+) changes. Infection of macrophages with Leishmania upregulated the expression of P2Y(2) and P2Y(4) receptor mRNA. The data suggest indirectly that Leishmania amazonensis infection induces modulation and heteromerization of P2Y receptors on macrophages. Thus UTP modulates the host response against L. amazonensis infection. UTP and UTP homologues should therefore be considered as novel components of therapeutic strategies against cutaneous leishmaniasis.
authors: Laboratory of Immunophysiology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro RJ, 21941-902, Brazil.
authors: Camila
authors: C
authors: Marques-da-Silva
authors: Mariana M
authors: MM
authors: Chaves
authors: Suzana Passos
authors: SP
authors: Chaves
authors: Vanessa Ribeiro
authors: VR
authors: Figliuolo
authors: José Roberto
authors: JR
authors: Meyer-Fernandes
authors: Suzana
authors: S
authors: Corte-Real
authors: Claudiana
authors: C
authors: Lameu
authors: Henning
authors: H
authors: Ulrich
authors: David M
authors: DM
authors: Ojcius
authors: Bartira
authors: B
authors: Rossi-Bergmann
authors: Robson
authors: R
authors: Coutinho-Silva
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase; D007891:Leishmania / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism; D011983:Receptors, Purinergic / Q000235:genetics / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D014544:Uridine Triphosphate