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

Haem from host erythrocyte (RBC) haemoglobin is polymerized in the digestiv e organelle of Plasmodium falciparum to haemozoin (HZ), a crystalline, inso luble substance. Human monocytes avidly ingest HZ that persists undigested for long periods of time, and generates potent bioactive lipid peroxide der ivatives. Protein kinase C, an effector of signal transduction, phagolysoso me formation and acidification, is inhibited in HZ-fed monocytes. Inability to digest HZ might derive from impairment in phagolysosome formation or ac idification. 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 pr eferentially present as separated particles, with full co-localization of r ed and green fluorescence. Later on HZ-laden phagolysosomes tended to fuse together. In conclusion, phagolysosome formation and acidification were nor mal in HZ-fed monocytes during the 72-h observation time. The presence of H Z in the phagolysosome, the site of antigen processing, may offer a physica l link with immunodepression in malaria.