Phagocytosis Of Hemozoin Prevents Human Monocyte Apoptosis: Role of Heat Shock Protein-27 in P. falciparum Malaria

Hemozoin (malarial pigment) is a crystalline ferriprotoporphyrin IX polymer present in late stages of P. falciparum-parasitized RBCs derived from incomplete digestion of host hemoglobin. Avidly phagocytosed hemozoin alters several functions of human monocytes, including bacterial killing, oxidative burst, antigen presentation; moreover, it produces increased amounts of peroxidation products of PUFAs and stimulates generation of several molecules such as TNF, IL-1beta and MMP-9 through NF-kB-dependent pathways. Here, apoptosis and protein expression of NF-kB-dependent HSP-27 and HSP-70 in hemozoin-fed human monocytes were studied. MATERIAL&METHODS: Cell survival, apoptosis and necrosis were measured either in adherent monocytes or suspendend THP-1 cell line by FACS analysis after propidium/annexin dying. Protein expression of HSP-27 and HSP-70 was evaluated by Western blotting. RESULTS: Apoptosis in both adherent or suspended mononuclear cells was not induced after 72 hours of phagocytosis of hemozoin, while it was already induced after 9 h of incubation with 10 uM gliotoxin, a potent pro-apoptotic molecule. Protein expression of anti-apoptotic HSP-27 was upregulated in hemozoin-fed adherent monocyte lysates, while was degraded in presence of gliotoxin. Pro-apoptotic HSP-70 expression was not altered. CONCLUSIONS: Present data suggest that apoptosis of hemozoin-fed monocytes is prevented through HSP-27 upregulation. Impaired mononuclear cells persist then in human blood leading to often lethal complicances of malaria.