Inhibition by reactive aldehydes of superoxide anion radical production in stimulated human neutrophils.
alpha,beta-Unsaturated aldehydes were investigated in vitro for their ability to inhibit superoxide anion radical (O2-.) production in stimulated human polymorphonuclear leukocytes (PMN). The aldehydes investigated were (i) trans-4-hydroxynonenal and malonaldehyde (MDA), two toxic lipid peroxidation products; (ii) acrolein and crotonaldehyde, two air pollutants derived from fossil fuel combustion; (iii) trans,trans-muconaldehyde, a putative hematotoxic benzene metabolite. Preincubation of PMN with reactive aldehydes followed by stimulation with the oxygen burst initiator phorbol myristate acetate (PMA) resulted in a dose-dependent inhibition of O2-. production. The concentration at which 50% inhibition (IC50) was observed was 21 microM for acrolein, 23 microM for trans,trans-muconaldehyde, 27 microM for trans-4-hydroxynonenal and 330 microM for crotonaldehyde. A similar inhibitory effect by these aldehydes was observed in digitonin- and concanavalin A-stimulated PMN. MDA inhibited O2-. production in PMA-stimulated PMN by 100% at 10(-2) M but gave no inhibition at 10(-3) M. The standard aldehyde propionaldehyde did not inhibit O2-. production at 10(-3)-10(-6) M. Preincubation of PMN with acrolein in the presence of cysteine completely protected against the inhibitory effect of this reactive aldehyde. The results indicate that the ability of toxic aldehydes to inhibit O2-. production in stimulated PMN correlates directly with their alkylation potential which is a function of the electrophilicity of the beta carbon.
Witz
G
G
Lawrie
N J
NJ
Amoruso
M A
MA
Goldstein
B D
BD
D000171:Acrolein / Q000494:pharmacology; D000447:Aldehydes / Q000494:pharmacology*; D000478:Alkylation; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation; D009504:Neutrophils / Q000378:metabolism*; D010101:Oxygen Consumption; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000447:Aldehydes; D008054:Lipid Peroxides; D013481:Superoxides; C034476:muconaldehyde; D000171:Acrolein; C012796:2-butenal; C027576:4-hydroxy-2-nonenal; D013755:Tetradecanoylphorbol Acetate