Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria
| العنوان: | Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria |
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| المؤلفون: | 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 |
| المصدر: | Nature Medicine. 13:703-710 |
| بيانات النشر: | Springer Science and Business Media LLC, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1546-170X 1078-8956 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c6fa8cc62ea6f71768ead3e028f0968Test https://doi.org/10.1038/nm1586Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....7c6fa8cc62ea6f71768ead3e028f0968 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1546170X 10788956 |
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