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Please use this identifier to cite or link to this item: http://repositorio.ufba.br/ri/handle/ri/13792

Title: Heme impairs prostaglandin E2 and TGF-β production by human mononuclear cells via Cu/Zn superoxide dismutase: insight into the pathogenesis of severe malaria
Other Titles: Journal of Immunology
Authors: Andrade, Bruno Bezerril
Santos, Théo Araújo
Luz, Nívea Farias
Cunha, Antônio Ricardo Khouri
Bozza, Marcelo Torres
Camargo, Luís Marcelo Aranha
Barral, Aldina Maria Prado
Borges, Valéria de Matos
Barral-Netto, Manoel
Issue Date: 2010
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 PGE2 and TGF-β 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 PGE2 and TGF-β than those with mild disease. In addition, there was a positive correlation between SOD-1 concentrations and plasma levels of TNF-α. During antimalaria treatment, the concentrations of plasma SOD-1 reduced whereas PGE2 and TGF-β 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 PGE2 and TGF-β 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.
Description: Texto completo: acesso restrito. p. 1196-1204
URI: http://repositorio.ufba.br/ri/handle/ri/13792
ISSN: 0022-1767
Appears in Collections:Artigos Publicados em Periódicos (Medicina)

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