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 N...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 <sup>51</sup>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<sup>+</sup>）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<sup>+</sup> P815 cells,which wasmediated by the perforin/granzyme pathway.展开更多
基金the grants 3.0053.92,3.0050.95,9.0038.96,1.5.411.98 from the National Foundation for Scientific Research(FWO)the grants 194.322.1740,195.332.1310,196.322.0140,and OZR.230 from the Research Council of the Free University of Brussels
文摘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 <sup>51</sup>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<sup>+</sup>）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<sup>+</sup> P815 cells,which wasmediated by the perforin/granzyme pathway.
