Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS

Author(s)

Pereira, Marcelo L. M. ; Ortolan, Luana S. ; Sercundes, Michelle K. ; Debone, Daniela ; Murillo, Oscar ; Lima, Flavia A. ; Marinho, Claudio R. F. ; Epiphanio, Sabrina

• Document type: Journal article
• Source: Mediators of Inflammation; v. 2016, p. 12-pg., 2016-01-01.

Abstract

Malaria is a serious disease, caused by the parasite of the genus Plasmodium, which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected with Plasmodium berghei ANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset ofMA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans. (AU)

• FAPESP's process: 12/10081-5 - The role heme oxygenase 1 in malaria-associated acute lung injury
• Grantee: Marcelo Luís Monteiro Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/53256-7 - Distress syndrome in a murine model associated to the severe malaria: a study of parasite-host interaction
• Grantee: Sabrina Epiphanio
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/09964-5 - The role of inflammasomes in the pathogenesis of malaria during pregnancy: effects and mechanisms
• Grantee: Cláudio Romero Farias Marinho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/20451-0 - The role of endothelial cells in the immunopathogenesis of murine malaria-associated ALI/ARDS: effects and mechanisms
• Grantee: Sabrina Epiphanio
• Support Opportunities: Regular Research Grants