Hemozoin and the human monocyte--a brief review of their interactions.
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.
Schwarzer
E
E
Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5 bis, 10126 Torino, Italy.
Skorokhod
O A
OA
Barrera
V
V
Arese
P
P
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000166:cytology; D004920:Erythropoiesis / Q000187:drug effects; D006420:Hemeproteins / Q000494:pharmacology / Q000502:physiology*; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D008288:Malaria / Q000097:blood / Q000469:parasitology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000469:parasitology; D010587:Phagocytosis / Q000187:drug effects; D010961:Plasmodium / Q000737:chemistry / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D034061:Thrombopoiesis / Q000187:drug effects
D001095:Arachidonic Acids; D016207:Cytokines; D006420:Hemeproteins; C020753:hemozoin; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate