%0 Journal Article
%T In Vivo Hemozoin Kinetics after Clearance of Plasmodium berghei Infection in Mice
%A Rosangela Frita
%A Daniel Carapau
%A Maria M. Mota
%A Thomas H£¿nscheid
%J Malaria Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/373086
%X Hemozoin (Hz) is released into the blood stream after rupture of infected red blood cells (iRBCs) at the end of each parasite replication cycle. This free Hz is ingested by circulating and resident phagocytes. The presence of Hz in tissues after clearance of infection has been previously reported. Still, little is known about the kinetics of Hz in vivo, during and after Plasmodium infection. It is particularly important to understand Hz kinetics after malaria infections as it has been reported that Hz is associated with impairment of immune functions, including possible consequences for coinfections. Indeed, if Hz remains biologically active for prolonged periods of time inside immunocompetent cells, the potential consequences of such accumulation and presence to the immune system should be clarified. Here, using several independent methods to assess the presence of Hz, we report the long-term in vivo kinetics of Hz in diverse organs in a murine model of malaria infection. 1. Introduction In malaria, at the end of each Plasmodium replication cycle, infected red blood cells (iRBCs) rupture and release merozoites, together with hemozoin (Hz), into the blood stream. At that stage, up to 80¨C90% of all haem iron is localized in the digestive food vacuole and more than 95% of this haem has been converted to Hz [1]. On the basis of these findings and other reports, it has been calculated that, on average, 0.2¨C2£¿grams of Hz are produced during each erythrocytic cycle, assuming a 1¨C10% parasitaemia [2, 3]. Hz is ingested by circulating and resident phagocytes. One study investigated the percentage of Hz-containing granulocytes and monocytes in circulation as a predictor of disease outcome [4], while another reported median half-lives of 72£¿hours for Hz-containing granulocytes and 216 hours for Hz-containing monocytes in circulation [5]. Although the prolonged presence of Hz in tissues of individuals that had suffered from Plasmodium infections has been reported since the 19th century [6, 7], little is known about the long-term kinetics of Hz in vivo. How and over what period is Hz ultimately eliminated? To our knowledge, only one study in mice tried to address this question using a fluorometric method [8]. This report showed that 70% of Hz disappeared from the liver over 270 days after parasite clearance, while the amount of Hz in the spleen increased 8-fold. The importance of understanding Hz kinetics lies in the reported effects of Hz in impairment of immunity [9¨C14], including possible consequences for coinfections, such as tuberculosis [15]. Moreover, if Hz
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