title: Biochemical model for inflammation of the brain: the effect of iron and transferrin on monocytes and lipid peroxidation.
abstract: Cerebral inflammation plays a role in diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), and depression. Iron is involved in infection and inflammation through free radical production. Theoretically transferrin should prohibit iron from participating in oxidative reactions, but transferrin has also been found to promote free radical damage. We reported previously that isolation of transferrin from plasma by ion exchange column chromatography produced a broad pink protein band that subsequently separated on a gel filtration column into three proteins containing many metals. In this study some properties of the three proteins were studied in 20 volunteers. Protein 3 (identified as transferrin by nephelometry) contained the most iron while Protein 1 (called "toxiferrin") contained significantly less iron (p < 0.00001). Plasma from volunteers obtained under conditions of infection/inflammation with fever (n = 5) had a significantly increased toxiferrin to transferrin ratio compared to healthy volunteers (n = 15; p < 0.001). In vitro, Protein 2 and transferrin inhibited lipid peroxidation, while toxiferrin (possibly a protease degradation product of transferrin), enhanced lipid peroxidation. Also, toxiferrin (1 mg/mL) caused a significant increase in viability of monocytes as measured by the 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) reduction test, as well as the morphological transformation of monocytes to macrophages.
authors.affiliation: Department of Chemical Pathology (National Health Laboratory Service), Tygerberg Hospital and Stellenbosch University, South Africa. sjvr@sun.ac.za
authors.forename: Susan J
authors.initials: SJ
authors.lastname: van Rensburg
authors.forename: Johann
authors.initials: J
authors.lastname: van Zyl
authors.forename: Dinie
authors.initials: D
authors.lastname: Hon
authors.forename: Willie
authors.initials: W
authors.lastname: Daniels
authors.forename: Jacobus
authors.initials: J
authors.lastname: Hendricks
authors.forename: Felix
authors.initials: F
authors.lastname: Potocnik
authors.forename: Rajiv
authors.initials: R
authors.lastname: Erasmus
mesh_terms: D000535:Aluminum / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002852:Chromatography, Ion Exchange; D003300:Copper / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005334:Fever / Q000276:immunology / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D013058:Mass Spectrometry; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014168:Transferrin / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism
chemical_list: D005609:Free Radicals; D014168:Transferrin; D003300:Copper; D000535:Aluminum; D007501:Iron; D015032:Zinc