Diminished organelle motion in murine Kupffer cells during the erythrocytic stage of malaria.
Parasitized erythrocytes are ingested by murine hepatic macrophages during malaria infection. We non-invasively monitored how this altered the motion of intracellular phagosomes in Kupffer cells using magnetometry. Submicrometric γFe(2)O(3) particles were injected prior to malaria infection. They were cleared from the blood, primarily by Kupffer cells, and retained within their phagosomes. The mice were periodically magnetized. After removing this external magnet, the aligned iron particles created a remnant magnetic field (RMF) which then decayed (relaxation), reflecting the motion of particle-containing phagosomes. After baseline measurements of relaxation, the mice were injected intravenously with Plasmodium chabaudi-parasitized or normal murine red blood cells (RBCs). During the next 15 days, relaxation measurements, parasitaemia and haematocrit values were monitored. At 6 days post injection with 3 × 10(7) parasitized RBCs, relaxation rates had decreased. At this time, all mice had parasitaemias greater than 58 per cent and haematocrits less than 20 per cent. At day 7, while the parasitaemias were declining, the rate of relaxation continued to decrease. Throughout the experiment, relaxation remained constant in animals injected with normal RBCs. Electron microscopy revealed Kupffer cells filled with damaged and parasitized erythrocytes, and haemoglobin degradation pigment. We conclude that ingestion and metabolism of parasitized erythrocytes by liver macrophages during malaria infection decreases their organelle motion with likely consequences of compromised host defences.
Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Charles F
CF
Bellows
Ramon M
RM
Molina
Joseph D
JD
Brain
D000818:Animals; D004195:Disease Models, Animal; D004574:Electromagnetic Fields; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006420:Hemeproteins / Q000737:chemistry; D007728:Kupffer Cells / Q000378:metabolism* / Q000469:parasitology*; D008264:Macrophages / Q000378:metabolism; D008288:Malaria / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron / Q000379:methods; D018512:Parasitemia / Q000097:blood; D010587:Phagocytosis; D010588:Phagosomes / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000378:metabolism
D006420:Hemeproteins; C020753:hemozoin