INVITRO EFFECTS OF PROTEASE INHIBITORS ON MURINE NATURAL-KILLER CELL-ACTIVITY

  • 1 January 1983
    • journal article
    • research article
    • Vol. 48  (1) , 1-8
Abstract
To test whether proteolytic events are involved in natural killer (NK) cell mediated lysis of tumor cells, 23 different protease inhibitors were added to in vitro assays of NK cell reactivity. Of the materials tested, only tosyl-L-lysine chloromethyl ketone (TLCK), tosyl-L-phenylalanine chloromethyl ketone (TPCK) and benzamidine uniequivocally inhibited killing at concentrations approaching those needed to affect appropriate purified proteases. All of the effective inhibitors, and none of the others tested, inhibited binding of effector to target cells. The action of TLCK was focused on both effector and target cells, in that cytolysis was completely inhibited by a 1-h pretreatment of effectors with 10-4 M TLCK and 60% inhibited by a 1-h treatment of targets only. The effect of TLCK on cytolysis could be prevented by a 1-h preincubation of the effector cell population with 10-2 M reduced glutathione. At 10-2 M, oxidized glutathione, dithiothreitol or cysteine could not abrogate the effect of 10-4 M TLCK. The action of reduced glutathione is complex, since lower concentrations of this reagent alone exhibit partial inhibition of NK cytolysis.