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Hemozoin and the human monocyte--a brief review of their interactions
E Schwarzer1, O A Skorokhod, V Barrera
1Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5 bis, 10126 Torino, Italy.
Abstract:
In vitro, human monocytes avidly ingest hemozoin (HZ) that 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 action: HZ generates by nonenzymatic catalysis large amounts of lipoperoxidation products, such as monohydroxy derivatives of arachidonic (HETE) and linoleic (HODE) acid, and 4-hydroxynonenal (HNE). Several HZ effects were reproduced by supplementation with plausible concentrations of HETE or HNE, the first most likely via interaction with PPAR-receptors, the second via adduct or crosslinks formation with critical targets.
Insights
Hemozoin (HZ) ingestion by human monocytes alters their function, inhibiting some activities while stimulating others. HZ generates lipoperoxidation products that mediate these diverse cellular effects.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Human monocytes avidly ingest hemozoin (HZ), a byproduct of malaria parasite metabolism.
- HZ interaction with monocytes leads to significant alterations in cellular functions.
Purpose of the Study:
- To investigate the functional consequences of hemozoin (HZ) uptake by human monocytes.
- To elucidate the mechanisms underlying HZ-mediated modulation of monocyte activities.
Main Methods:
- In vitro incubation of human monocytes with hemozoin (HZ).
- Assessment of various monocyte functions, including respiratory burst, phagocytosis, enzyme activity, and cell surface marker expression.
- Analysis of lipoperoxidation products and their role in HZ effects, including supplementation studies with HETE and HNE.
Main Results:
- HZ inhibited PMA-elicited respiratory burst, killing and repeat phagocytosis, NADPH-oxidase and PKC activity, ICAM-1, integrin-CD11c, and MHC-class-II expression.
- HZ also inhibited differentiation into functional, antigen-presenting dendritic cells.
- Conversely, HZ increased phagocytosis-related respiratory burst, lipoperoxidation product accumulation, metalloproteinase-9, and pro-inflammatory cytokines/chemokines.
Conclusions:
- Hemozoin (HZ) exerts dual effects on human monocytes, inhibiting key immune functions while stimulating others.
- HZ-generated lipoperoxidation products, such as HETE and HNE, are critical mediators of these effects, potentially via PPAR-receptor interaction or adduct formation.
