Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria
| Autor: | Maria M. Mota, Cristina Rodrigues, Viktória Jeney, Isabel Pombo Gregoire, Silvia Portugal, Sabrina Epiphanio, Miguel P. Soares, Ana Ferreira, Margarida Cunha-Rodrigues, György Balla, Ângelo Chora, József Balla, Ana Pamplona |
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| Rok vydání: | 2007 |
| Předmět: |
HMOX1
Plasmodium berghei Malaria Cerebral Heme Mice SCID Parasitemia Pharmacology Klinikai orvostudományok General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound parasitic diseases Animals Medicine Mice Knockout Carbon Monoxide Mice Inbred BALB C biology business.industry Orvostudományok General Medicine biology.organism_classification medicine.disease Mice Inbred C57BL Heme oxygenase Transplantation Disease Models Animal chemistry Cerebral Malaria Immunology Hemoglobin business Heme Oxygenase-1 |
| Zdroj: | Nature Medicine. 13:703-710 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Cerebral malaria claims more than 1 million lives per year. We report that heme oxygenase-1 (HO-1, encoded by Hmox1) prevents the development of experimental cerebral malaria (ECM). BALB/c mice infected with Plasmodium berghei ANKA upregulated HO-1 expression and activity and did not develop ECM. Deletion of Hmox1 and inhibition of HO activity increased ECM incidence to 83% and 78%, respectively. HO-1 upregulation was lower in infected C57BL/6 compared to BALB/c mice, and all infected C57BL/6 mice developed ECM (100% incidence). Pharmacological induction of HO-1 and exposure to the end-product of HO-1 activity, carbon monoxide (CO), reduced ECM incidence in C57BL/6 mice to 10% and 0%, respectively. Whereas neither HO-1 nor CO affected parasitemia, both prevented blood-brain barrier (BBB) disruption, brain microvasculature congestion and neuroinflammation, including CD8(+) T-cell brain sequestration. These effects were mediated by the binding of CO to hemoglobin, preventing hemoglobin oxidation and the generation of free heme, a molecule that triggers ECM pathogenesis. |
| Databáze: | OpenAIRE |
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