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Effects of Malaria Heme Products on Red Blood Cell Deformability

In falciparum malaria, the deformability of the entire erythrocyte population is reduced in proportion to disease severity, and this compromises microcirculatory blood flow through vessels partially obstructed by cytoadherent parasitized erythrocytes. The cause of rigidity of uninfected erythrocytes in not known but could be mediated by malaria heme products. In this study, we show that red blood cell deformability (RBC-D), measured by laser-assisted optical rotational cell analyzer, decreased in a dose-dependent manner after incubation with hemin and hydrogen peroxide but not with hemoglobin or ß-hematin. Hemin also reduced mean red cell volume. Albumin decreased and N-acetylcysteine (NAC) both prevented and reversed rigidity induced by hemin. Hemin-induced oxidative damage of the membrane seems to be a more important contributor to pathology than cell shrinkage because the antioxidant NAC restored RBC-D but not red blood cell volume. The findings suggest novel approaches to the treatment of potentially lethal malaria.

Received December 22, 2006. Accepted for publication June 26, 2007.

Acknowledgment: The authors thank Dr. Wirichada Pongthavonpinyo for her helpful statistical discussion.

Financial support: This study was supported by the Wellcome Trust of Great Britain. N.J.W. is a Wellcome Trust Principal Fellow.

^* Address correspondence to Arjen M. Dondorp, Mahidol–Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. E-mail: arjen{at}tropmedres.ac

Authors’ addresses: Forradee Nuchsongsin, Kesinee Chotivanich, Prakaykaew Charunwatthana, Nicholas P. Day, Nicholas J. White, and Arjen M. Dondorp, Mahidol–Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand, Telephone: +66 (0)2 3549170, Fax: +66 (0)2 3549169, E-mail: arjen{at}tropmedres.ac. Fausta Omodeo-Salè, Institute of General Physiology and Biochemistry, University of Milan, Via Pascal 36, 20133 Milano, Italy, Telephone: +39 02 503 15780, Fax: +39 02 503 15775, E-mail: fausta.omodeosale{at}unimi.it. Donatella Taramelli, Department of Public Health–Microbiology–Virology, University of Milan, Via Pascal 36, 20133 Milano, Italy, Telephone: +39 02 503 15071, Fax: +39 02 503 15068, E-mail: donatella.taramelli{at}unimi.it.