Inhibition of neutrophil sulfhydryl groups by choloromethyl ketones. A mechanism for their inhibition of superoxide production.
The inhibition of O2- production by serine protease inhibitors such as chloromethyl ketone derivatives, has been used as evidence to indicate that protease activity is essential for the production of O2- by neutrophils. However, chloromethyl ketones are potent inhibitors of sulfhydryl groups. This study demonstrates that chloromethyl ketones inhibited non-protein sulfhydryl groups as well as O2- production by human neutrophils stimulated with phorbol myristate acetate (PMA). Their inhibition of O2- production could be prevented by reduced glutathione. The results suggest that inhibition of O2- production by chloromethyl ketones is largely due to their inhibition of sulfhydryl groups.
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000097:blood*; D013438:Sulfhydryl Compounds / Q000037:antagonists & inhibitors* / Q000097:blood; D013481:Superoxides / Q000097:blood*; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D013438:Sulfhydryl Compounds; D013481:Superoxides; D007531:Isoflurophate; D014107:Tosyllysine Chloromethyl Ketone; D014108:Tosylphenylalanyl Chloromethyl Ketone; D005033:Ethylmaleimide; D010100:Oxygen