title: The effects of increased heme oxygenase-1 on the lymphoproliferative response in dogs with visceral leishmaniasis.
abstract: Canine visceral leishmaniasis (CVL) is known to affect the cellular immunity of infected dogs, through impairing lymphoproliferation and microbicidal mechanisms. This study examined heme oxygenase-1 (HO-1) and its metabolites, oxidative stress and IL-10 levels in CVL and investigated correlations between these parameters. Additionally, the effects of HO-1 inhibition on the lymphoproliferative response and cytokine production in lymph node cells (LNCs) from infected dogs were evaluated. Forty-four dogs, 24 controls and 20 dogs with CVL were selected. Plasma and splenic levels of HO-1, haptoglobin, soluble CD163 receptor, ferritin and IL-10 were determined using capture ELISA. The HO-1 levels and relative gene expression in peripheral blood and bone marrow mononuclear cells were also determined. LNCs proliferation was evaluated with an HO-1 activator and with an HO-1 inhibitor, in the presence of the Leishmania infantum soluble antigen (SAgL), using flow cytometry. HO-1, IL-2, IFN-gamma and IL-10 were also determined in these cultures using capture ELISA. Infected dogs presented oxidative stress and increased HO-1 levels and relative gene expression, with correlation between oxidative stress and HO-1. The substances from heme metabolism and IL-10 were also elevated in the plasma and spleens of infected dogs. IL-10 and HO-1 levels were positively correlated with one another. Inhibition of HO-1 increased LNCs proliferation and decreased IL-10 and IL-2 production in the presence of SAgL. The increased HO-1 metabolism observed in CVL is probably associated with oxidative stress and increased IL-10, which could be one of the mechanisms responsible for inhibition of the lymphoproliferative response in sick dogs.
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil. Electronic address: bfmalmeida@yahoo.com.br.
authors.forename: Breno Fernando Martins de
authors.initials: BF
authors.lastname: Almeida
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Kathlenn Liezbeth Oliveira
authors.initials: KL
authors.lastname: Silva
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Vanessa Marim
authors.initials: VM
authors.lastname: Chiku
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Aline Aparecida Correa
authors.initials: AA
authors.lastname: Leal
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Gabriela Lovizutto
authors.initials: GL
authors.lastname: Venturin
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Luis Gustavo
authors.initials: LG
authors.lastname: Narciso
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Maria Fernanda Cereijido Bersni
authors.initials: MF
authors.lastname: Fink
authors.affiliation: Department of Animal Internal Medicine, Surgery and Reproduction, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Flavia de Rezende
authors.initials: FR
authors.lastname: Eugênio
authors.affiliation: Department of Animal Internal Medicine, Surgery and Reproduction, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Paulo Sergio Patto Dos
authors.initials: PS
authors.lastname: Santos
authors.affiliation: Department of Animal Internal Medicine, Surgery and Reproduction, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Ciarlini
authors.affiliation: Immunology Laboratory, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil; Department of Animal Internal Medicine, Surgery and Reproduction, São Paulo State University (Unesp), School of Veterinary Medicine, Rua Clovis Pestana 793, Araçatuba, São Paulo, CEP 16050-680, Brazil.
authors.forename: Valéria Marçal Felix de
authors.initials: VM
authors.lastname: Lima
mesh_terms: D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004283:Dog Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D004285:Dogs; D004909:Erythrocyte Indices; D005260:Female; D015870:Gene Expression; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000662:veterinary*; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D053858:Metabolic Networks and Pathways; D009928:Organ Specificity / Q000235:genetics; D018384:Oxidative Stress; D059208:Parasite Load
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006418:Heme; D051547:Heme Oxygenase-1
keywords: Canine; HSP32; Leishmania infantum; Lymphoproliferation