title: Mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by Plasmodium berghei NK65 infection.
abstract: Infection of mice with Plasmodium berghei NK65 represents a well-recognized malaria model in which infection is accompanied by an intense hepatic inflammatory response. Enzyme-inducible nitric oxide synthase is an important regulator of inflammation and leukocyte recruitment in microvessels, but these functions have yet to be evaluated in experimental malaria. In this study, we assessed the involvement of inducible nitric oxide synthase in inflammatory responses to murine experimental malaria induced by P. berghei NK65. We observed that wild type (WT) and nitric oxide synthase (iNOS)-deficient mice (iNOS(-/-)) mice showed similar levels of parasitemia following P. berghei NK65 infection, although infected iNOS(-/-) mice presented early mortality. Inducible nitric oxide synthase deficiency led to increased leukocyte rolling and adhesion to the liver in iNOS(-/-) mice relative to the WT animals, as observed via intravital microscopy. Infected iNOS(-/-) mice also exhibited increased hepatic leukocyte migration and subsequent liver damage, which was associated with high serum levels of the cytokines TNF-α, IL-6 and IL-10. Our data suggest potential role for the iNOS enzyme as a regulator of hepatic inflammatory response induced by P. berghei NK65-infection, and its absence leads to exacerbated inflammation and sequential associated-hepatic damage in the animals.
authors.affiliation: Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Onésia Cristina
authors.initials: OC
authors.lastname: Oliveira-Lima
authors.forename: Danielle
authors.initials: D
authors.lastname: Bernardes
authors.forename: Mauro Cunha
authors.initials: MC
authors.lastname: Xavier Pinto
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Esteves Arantes
authors.forename: Juliana
authors.initials: J
authors.lastname: Carvalho-Tavares
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D006505:Hepatitis / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008288:Malaria / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000276:immunology*; D010962:Plasmodium berghei / Q000276:immunology* / Q000472:pathogenicity; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D052247:Nitric Oxide Synthase Type II
keywords: Experimental malaria; Inducible nitric oxide synthase; Inflammation; Leukocyte recruitment; Liver