Ferritin-dependent lipid peroxidation by stimulated neutrophils: inhibition by myeloperoxidase-derived hypochlorous acid but not by endogenous lactoferrin.
Human neutrophils stimulated with phorbol myristate acetate or formylmethionylleucylphenylalanine caused superoxide-dependent release of iron from feritin, measured as the formation of a ferrous-ferrozine complex. The stimulated cells also caused ferritin-dependent peroxidation of phospholipid liposomes. Peroxidation was inhibited by lactoferrin, but only at concentrations considerably in excess of what could be achieved by release of endogenous lactoferrin. Peroxidation was enhanced by catalase and methionine, especially when stimulants that release myeloperoxidase were used. Peroxidation was inhibited by added myeloperoxidase. These results are explained by myeloperoxidase catalysing the formation of hypochlorous acid (HOCl) and the HOCl reacting with the lipid to inhibit peroxidation. Thus, neutrophils are able to use ferritin to promote lipid peroxidation. This may be limited under some conditions by iron binding to lactoferrin or transferrin, and more generally by reactions of the lipid with myeloperoxidase-derived HOCl. However, the latter reactions themselves may be harmful.
Winterbourn
C C
CC
Department of Pathology, School of Medicine, Christchurch Hospital, New Zealand.
Monteiro
H P
HP
Galilee
C F
CF
D005293:Ferritins / Q000097:blood*; D006801:Humans; D006997:Hypochlorous Acid / Q000097:blood*; D007501:Iron / Q000097:blood; D007700:Kinetics; D007781:Lactoferrin / Q000097:blood* / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008081:Liposomes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006997:Hypochlorous Acid; D005293:Ferritins; D007501:Iron; D009195:Peroxidase; D007781:Lactoferrin; D013755:Tetradecanoylphorbol Acetate