Beyond heme detoxification: A role for hemozoin in iron transport in S. japonicum

Abstract

Hemozoin (Hz) is considered a disposal product during the digestion of red blood cells by some blood-feeding parasites, such as Plasmodium, Schistosome, and Rhodnius. The only function of Hz that has been reported is to detoxify the free heme (Fe(III)-protoporphyrin-IX) in worms. Here we report a new role for Hz in iron transport in Schistosoma japonicum. Using transmission electron microscopy (TEM), we observed that S. japonicum hemozoin (sjHz) granules were a group of electron-dense, globe-, and comma-shaped granules. At the anterior end of female worm gut, these dark brown granules were found to be mixed with biconcave disc-shaped erythrocytes, in the middle portion of the gut these granules attached to destroyed erythrocytes and in the posterior portion of the gut no intact erythrocytes were observed except free sjHz granules. By energy dispersive spectroscopy (EDS) and Prussian blue iron staining, we found that these iron-containing sjHz granules are degraded near the microvilli adjacent to vitelline glands, resulting in the accumulation of a large amount of iron in the vitelline cells and eggs of developed S. japonicum. The accumulation of iron in vitelline glands was synchronized with the increase of sjHz granules in the gut. When S. japonicum just contained a little amount of sjHz granules in gut, hardly any accumulation of iron was detected in vitelline glands. However, when the lumen of gut filled full with sjHz granules, large amounts of iron was detected in vitelline glands. Solexa sequencing revealed that expression of iron store protein, ferritin-1 (CAX77379.1), is just significantly up-regulated in worms that contained a large amount of sjHz in gut. In contrast to the idea that sjHz granules are simply by-product of heme detoxification, we found that formation and degradation of sjHz granules in vivo likely serve for the iron transport. Our findings provide new insights into the biological significance of Hz formation. © 2013 Springer-Verlag Berlin Heidelberg.