Mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by Plasmodium berghei NK65 infection |
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| Institution: | 1. 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;2. Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Professor Alfredo Balena, 190, Santa Efigênia, Belo Horizonte, MG 30130-100, Brazil;3. Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil;1. Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA;2. Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA;1. Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Building 224, DK-2800 Kgs. Lyngby, Denmark;2. Department of Microbiology and Risk Assessment, The National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark;3. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Copenhagen University, Ridebanevej 9, DK-1871 Frederiksberg C, Denmark;1. Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain;2. Department of Regenerative Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain;3. NIMGenetics SL, 28049 Madrid, Spain;4. Animal Unit, Fundación Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain;5. Centro de Biología Molecular Severo Ochoa (CBMSO), 28049 Madrid, Spain;1. Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria;2. Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria;3. The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel;4. The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;1. Laboratory of Inflammation, Gestation and Autoimmunity, Jacques Monod Institute, CNRS and University Paris-Diderot, 15 rue Hélène Brion, 75205 Paris Cedex 13, France;2. Centre d''Immunologie de Marseille-Luminy (CIML), Aix-Marseille University UM2, France;3. INSERM U1104 and CNRS UMR7280, Marseille, France;4. Health Sciences Research Institute and School of Natural Sciences, University of California, 5200 North Lake Road, Merced, CA 95343, USA |
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| 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. |
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| Keywords: | Inflammation Leukocyte recruitment Experimental malaria Inducible nitric oxide synthase Liver |
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