Interactions between hemozoin and the human monocyte-Brief review

In vitro, human monocytes avidly ingest hemozoin (HZ) corresponding to approx. 10 RBC-equivalents/monocyte. HZ modifies a number of monocyte functions. Inhibitory effects: inhibition of: PMA-elicited respiratory burst, ability to killing and repeat phagocytosis, activity of NADPH-oxidase and PKC, expression of ICAM-1, integrin-CD11c, MHC-class-II (IFN-gamma-mediated), differentiation to functional antigen presenting dendritic cells. Stimulatory effects: increase in phagocytosis-related respiratory burst and accumulation of lipoperoxidation products; induction of metalloproteinase-9 and pro-inflammatory cytokines and chemokines. Mechanism of HZ action: HZ generates by non-enzymatic heme-catalysis and lipid peroxidation large amounts of potent HETEs, HODEs, and 4-hydroxynonenal [HNE]). HZ effects were largely reproduced by 12/15-HETE or HNE, the first most likely via interaction with PPAR-receptors, the second via adduct formation with critical targets.