Phagocytosis of malarial pigment haemozoin by human monocytes: a confocal microscopy study

Abstract

Haem from host erythrocyte (RBC) haemoglobin is polymerized in the digestive organelle of Plasmodium falciparum to haemozoin (HZ), a crystalline, insoluble substance. Human monocytes avidly ingest HZ that persists undigested for long periods of time, and generates potent bioactive lipid peroxide derivatives. Protein kinase C, an effector of signal transduction, phagolysosome formation and acidification, is inhibited in HZ-fed monocytes. Inability to digest HZ might derive from impairment in phagolysosome formation or acidification. Time-course and extent of HZ phagocytosis and acidification of phagolysosomes were studied by quantitative confocal microscopy. From 180 min until 72 h after the start of phagocytosis approximately 75–79% of the monocytes contained massive amounts of HZ. Coincidence between red (HZ) and green (acidic organelles) fluorescent compartments was very high. Confocal images showed that at 30–60 min after the start of phagocytosis, HZ was preferentially present as separated particles, with full co-localization of red and green fluorescence. Later on HZ-laden phagolysosomes tended to fuse together. In conclusion, phagolysosome formation and acidification were normal in HZ-fed monocytes during the 72-h observation time. The presence of HZ in the phagolysosome, the site of antigen processing, may offer a physical link with immunodepression in malaria.