Studies on the mechanism of NK cell lysis.
The mechanism of cytolysis by murine NK cells was analyzed using a variety of metabolic inhibitors that have proven informative in studying the lytic mechanism of CTL and the mechanism of histamine release by mast cells. Target cell binding occurred in the absence of calcium and was inhibited by only one of the agents studied, cytochalasin B. Lysis was initiated by addition of Ca2+ ions, as in the case of CTL. Subsequent to target cell binding, but prior to programming for lysis by Ca2+, NK cell lytic activity could be suppressed by inhibitors of chymotrypsin-like, but not trypsin-like proteases, in contrast to CTL. In addition, 3-deaza-SIBA, an inhibitor of transmethylation reactions and quinacrine, an inhibitor of phospholipase A2, appear to act before the Ca2+-dependent programming for lysis. Sr2+ ions blocked the lytic function, as did trifluoperazine (stelazine), the former presumably competing for ionic calcium, the latter known to block binding of Ca2+ to calmodulin. 8Br-cAMP and colchicine blocked later steps required for lysis. With the possible exception of trifluoperazine, all of the agents that blocked NK cell lysis are known to inhibit histamine release from mast cells. These results lend support to the stimulus-secretion model, originally proposed to explain the mechanism of CTL cytolysis, as relevant to the mechanism of lysis by NK cells.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007111:Immunity, Cellular; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009579:Nitrobenzoates / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D048448:Phenylcarbamates; D011480:Protease Inhibitors / Q000494:pharmacology*; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D002219:Carbamates; D007211:Indoles; D009579:Nitrobenzoates; D048448:Phenylcarbamates; D011480:Protease Inhibitors; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D014107:Tosyllysine Chloromethyl Ketone; C026868:N-acetylphenylalanine ethyl ester; D014108:Tosylphenylalanyl Chloromethyl Ketone; D014443:Tyrosine; D010649:Phenylalanine; C017194:5'-deoxy-5'-(isobutylthio)-3-deazaadenosine; C007651:ethyl N-alpha-acetyl-tyrosinate; C030374:indole; D001120:Arginine; C012208:benzoyl L-arginine methyl ester; D014372:Tubercidin; D002118:Calcium