REAL

Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria.

Pamplona, A. and Ferreira, A. and Balla, József and Jeney, Viktória and Balla, György (2007) Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. NATURE MEDICINE, 13. pp. 703-710. ISSN 1078-8956

[img] Text
1239490.pdf
Restricted to Registered users only

Download (371kB) | Request a copy

Abstract

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.

Item Type: Article
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat
R Medicine / orvostudomány > RJ Pediatrics / gyermekgyógyászat
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 03 Jun 2014 11:56
Last Modified: 03 Jun 2014 11:56
URI: http://real.mtak.hu/id/eprint/12971

Actions (login required)

Edit Item Edit Item