AIM Several triggering receptors have beendescribed to be involved in natural killer(NK)cell-mediated target cytotoxicity.In these studies,NKcells derived from blood or spleen were used.Pitcells are liver-specific NK cells that possess ahigher level of natural cytotoxicity and a differentmorphology when compared to blood NK cells.The aim of this study was to characterize the roleof the NK-triggering molecules NKR-P1A,ANK61antigen,and CD45 in pit cell-mediated killing oftarget cells.METHODS ~(51)Cr-release and DNA fragmentationwere used to quantify target cell lysis andapoptosis,respectively.RESULTS Flow cytometric analysis showed thatpit cells expressed CD45,NKR-P1A,and ANK61antigen.Treatment of pit cells with monoclonalantibody(mAb)to CD45(ANK74)not onlyinhibited CC531s or YAC-1 target lysis but alsoapoptosis induced by pit cells.The mAbs to NKR-P1A(3.2.3)and ANK61 antigen(ANK61)had no effect on pit cell-mediated CC531s or YAC-1 targetcytolysis or apoptosis,while they did increase theFcγ receptor positive(FcγR~+)P815 cytolysis andapoptosis.This enhanced cytotoxicity could beinhibited by 3,4-dichloroisocoumarin,an inhibitorof granzymes.CONCLUSION These results indicate that CD45participates in pit cell-mediated CC531s and YAC-1target cytolysis and apoptosis.NKR-P1A andANK61 antigen on pit cells function as activationstructures against FcγR~+ P815 cells,which wasmediated by the perforin/granzyme pathway. AIM Several triggering receptors have beencribed to be involved in natural killer (NK) cell-mediated target cytotoxicity. In these studies, NK cells derived from blood or spleen were used. Pitcells are liver-specific NK cells that possess ahigher level of natural cytotoxicity and a differentmorphology when compared to blood NK cells. The aim of this study was to characterize the roleof the NK-triggering molecules NKR-P1A, ANK61antigen, and CD45 in pit cell-mediated killing oftarget cells. METHODS ~ (51) Cr-release and DNA Fragmentationwere used to quantify target cell lysis andapoptosis, respectively.RESULTS Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1A, and ANK61antigen. Treatment of pit cells with monoclonalantibody (mAb) to CD45 (ANK74) not only inhibited CC531s or YAC-1 target lysis but alsoapoptosis induced by pit cells.The mAbs to NKR-P1A (3.2.3) and ANK61 antigen (ANK61) had no effect on pit cell-mediated CC531s or YAC-1 targetcytolysis or apoptosis, while they did increase the Fcγ receptor positive (FcγR ~ +) P815 cytolysis andapoptosis.This enhanced cytotoxicity could be inhibited by 3,4-dichloroisocoumarin, an inhibitor of granzymes. CONCLUSION These results indicate that CD45participates in pit cell-mediated CC531s and YAC-1target cytolysis and apoptosis. NKR- P1A andANK61 antigen on pit cells function as activationstructures against FcγR ~ + P815 cells, which wasmediated by the perforin / granzyme pathway.