Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7534
Title: Heme impairs prostaglandin E2 and TGF-beta production by human mononuclear cells via Cu/Zn superoxide dismutase: insight into the pathogenesis of severe malaria
Authors: Andrade, Bruno de Bezerril
Santos, Théo de Araújo
Luz, Nívea Farias
Khouri, Ricardo
Bozza, Marcelo Torres
Camargo, Luis M
Barral, Aldina Maria Prado
Borges, Valeria de Matos
Barral Netto, Manoel
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Abstract: In many hemolytic disorders, such as malaria, the release of free heme has been involved in the triggering of oxidative stress and tissue damage. Patients presenting with severe forms of malaria commonly have impaired regulatory responses. Although intriguing, there is scarce data about the involvement of heme on the regulation of immune responses. In this study, we investigated the relation of free heme and the suppression of anti-inflammatory mediators such as PGE(2) and TGF-beta in human vivax malaria. Patients with severe disease presented higher hemolysis and higher plasma concentrations of Cu/Zn superoxide dismutase (SOD-1) and lower concentrations of PGE(2) and TGF-beta than those with mild disease. In addition, there was a positive correlation between SOD-1 concentrations and plasma levels of TNF-alpha. During antimalaria treatment, the concentrations of plasma SOD-1 reduced whereas PGE(2) and TGF-beta increased in the individuals severely ill. Using an in vitro model with human mononuclear cells, we demonstrated that the heme effect on the impairment of the production of PGE(2) and TGF-beta partially involves heme binding to CD14 and depends on the production of SOD-1. Aside from furthering the current knowledge about the pathogenesis of vivax malaria, the present results may represent a general mechanism for hemolytic diseases and could be useful for future studies of therapeutic approaches.
DeCS: Dinoprostona
Heme
Leucócitos Mononucleares
Superóxido Dismutase
Fator Transformador de Crescimento beta
Malaria
Issue Date: 2010
Citation: ANDRADE, B. B. et al. Heme impairs prostaglandin E2 and TGF-beta production by human mononuclear cells via Cu/Zn superoxide dismutase: insight into the pathogenesis of severe malaria. Journal of Immunology, v.185, n.2, p.1196-1204, 2010.
DOI: 10.4049/jimmunol.0904179
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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