Superoxide production by human eosinophils can be inhibited in an agonist-selective manner.
This paper focuses on eosinophil activation and its selective inhibition. Superoxide anion (O2-) production by human eosinophils, an indicator of their activation, was induced by a variety of activators. Several compounds which are known to inhibit protein kinase C (staurosporine, K252a, sphingosine) inhibited O2- production induced by phorbol ester (PMA) but failed to inhibit O2- production induced by IgG coupled to Sepharose beads. Inhibition of O2- production by other agents (plasma-activated zymosan, fMLP, and leukotriene B4 (LTB4), was intermediate. By contrast, wortmannin, a compound which has been previously reported to inhibit O2- production in neutrophils via a protein kinase-independent pathway, potently inhibited O2- production in eosinophils which had been activated by IgG and by Platelet-Activating Factor but was virtually inactive against PMA-induced O2- production. Taken together, the results indicate that, as a minimum, there must be two pathways of induction of O2- production in eosinophils. Moreover, the intermediate levels of inhibition in cells which had been activated with serum-activated zymosan, FMLP, and LTB4 suggest that these agents may either be acting via both of these pathways or that yet other pathways may exist.
Bach
M K
MK
Hypersensitivity Diseases, Drug Metabolism Research and Clinical Pharmacology, Upjohn Laboratories, Kalamazoo, MI 49001.
Brashler
J R
JR
Petzold
E N
EN
Sanders
M E
ME
D000470:Alkaloids / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G; D026121:Indole Alkaloids; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin; D015054:Zymosan / Q000494:pharmacology
D000470:Alkaloids; D000730:Androstadienes; D002227:Carbazoles; D007074:Immunoglobulin G; D026121:Indole Alkaloids; D010972:Platelet Activating Factor; D013481:Superoxides; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; C049985:staurosporine aglycone; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin