Hydroxy radical as autotoxin in chemotactically activated neutrophils.
Chemotactic stimulation of neutrophils can result in the production and release of toxic oxygen metabolites which, in turn, may affect neutrophil function. We have investigated the effects of catalase, superoxide dismutase, hydroxyl radical scavengers and a iron chelator on chemotactic responses of rat peritoneal neutrophils in vitro. Neutrophils were quantitatively assessed in micropore filters for chemotactic migration to several different chemotactic peptides including C5a, present in inulin-activated rat serum, the non-oxidizable tripeptide N-formyl-norleucyl-leucyl-phenylalanine, and the oxidizable peptide N-formyl-methionyl-leucyl-phenylalanine. The presence of catalase in the suspension of neutrophils caused a dose-dependent enhancement of chemotactic responses to each of the three chemotactic stimuli, whereas addition of superoxide dismutase had little effect. Hydroxyl radical scavengers (mannitol, dimethyl sulfoxide) or the iron chelator, deferoxamine, also afforded significant, dose-dependent enhancement of neutrophyl chemotaxis, while the iron-saturated chelator was devoid of chemotaxis-enhancing properties. Furthermore, stimulation of rat neutrophils with phorbol myristate acetate resulted in the appearance of products of lipid peroxidation (conjugated Schiff bases), the generation of which could be prevented by the hydroxyl radical scavenger, dimethyl thiourea. These data suggest that catalase, hydroxyl radical scavengers, and iron chelators protect chemotactically stimulated neutrophils from autotoxicity caused by neutrophil-derived hydrogen peroxide and its iron-catalyzed conversion product, hydroxyl radical.
Till
G O
GO
Department of Pathology, University of Michigan, Medical School, Ann. Arbor.
Lutz
M J
MJ
Ward
P A
PA
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003182:Complement C5 / Q000502:physiology; D015936:Complement C5a; D003676:Deferoxamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism / Q000494:pharmacology*; D017665:Hydroxyl Radical; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003182:Complement C5; D006878:Hydroxides; D008054:Lipid Peroxides; D009842:Oligopeptides; D017665:Hydroxyl Radical; D008353:Mannitol; D009240:N-Formylmethionine Leucyl-Phenylalanine; C024998:N-formylnorleucyl-leucyl-4-phenylalanine; D015936:Complement C5a; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide