Evidence for involvement of serine proteases in the late stages of the natural killer cell lytic reaction.
An irreversible inhibitor (L-1-tosylamide-2-phenylethyl-chloromethylketone) and substrate (N-acetyl-L-tyrosineethylester) of the neutral serine protease chymotrypsin were evaluated for their effects on the natural killer cell lytic reaction sequence. During direct cell-mediated cytolysis these inhibitors had no effect on natural killer cell binding to target cells but were able to inhibit the "trigger" mechanism which initiates killing. In addition, they inhibited later calcium-dependent events in the lytic reaction and killer cell-independent lysis. These findings suggest that serine proteases may be required during several stages of natural killer cell lysis, including calcium-dependent programming as well as the actual lethal hit.
D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D010450:Endopeptidases / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D012697:Serine Endopeptidases; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D014108:Tosylphenylalanyl Chloromethyl Ketone; D014443:Tyrosine; C007651:ethyl N-alpha-acetyl-tyrosinate; D010450:Endopeptidases; D012697:Serine Endopeptidases; D002118:Calcium