Mesh : Animals Arachidonic Acids / blood Cell Differentiation / drug effects Cytokines / blood Dendritic Cells / cytology Erythropoiesis / drug effects Hemeproteins / pharmacology physiology Host-Parasite Interactions / physiology Humans Malaria / blood parasitology Matrix Metalloproteinase 9 / metabolism Monocytes / drug effects enzymology parasitology Phagocytosis / drug effects Plasmodium / chemistry physiology Respiratory Burst / drug effects Tetradecanoylphorbol Acetate / pharmacology Thrombopoiesis / drug effects

来  源:   DOI:

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.
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