Levels Of Natural Cytotoxicity Research Articles

Participation of CD45, NKR-P1A and ANK61 antigen in rat hepatic NK cell (pit cell)mediated target cell cytotoxicity.

AIM:Several triggering receptors have been described to be involved in natural killer (NK) cell-mediated target cytotoxicity. In these studies, NK cells deriv ed from blood or spleen were used. Pit cells are liver-specific NK cells that possess a higher level of natural cytotoxicity and a different morphology when compared to blood NK cells. The aim of this study was to characterize the role of the NK triggering molecules NKR P1A, ANK61 antigen, and CD45 in pit cell medi ated killing of target cells.METHODS:( 51) Crrelease and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively.RESULTS:Flow cytometric analysis showed that pit cells expressed CD45, NK R P1A, and ANK61 antigen. Treatment of pit cells with monoclonal antibody (mAb)to CD45 (ANK74) not only inhibited CC531s or YAC 1 target lysis but also apopt osis 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 target cytolysis or apopto sis, while they did increase the Fcgamma receptor positive (FcgammaR(+)) P815 cytolysi s and apoptosis. This enhanced cytotoxicity could be inhibited by 3,4 dichloroi socoumarin, an inhibitor of granzymes.CONCLUSION:These results indicate that CD45 participates in pit cell med iated CC531s and YAC-1 target cytolysis and apoptosis. NKR-P1A and ANK61 antigen on pit cells function as activation structures against Fc gammaR( +) P 815 cells, which was mediated by the perforin/granzyme pathway.

Recovery of Natural Cytotoxicity After Bone Marrow Transplantation

Reconstitution of non-MHC restricted cytotoxicity was followed in 7 and in 4 cases after auto- and allotransplantation, respectively. In autografted cases a high level of natural cytotoxicity, which exceeded the pre-transplant values, was seen at the beginning of hematological reconstitution. At that time, the high percentage of DR+ peripheral blood mononuclear cells (PBMC) was found, while the percentage of CD16+ cells was in the range of the pre-transplant values. A high level of cytotoxicity was a transient phenomenon. In all cases, 40 days after grafting the natural cytotoxicity was again in the range of the pre-transplant values. In allotransplantation the peak of cytotoxicity was seen soon after the beginning of hematological recovery and the activity decreased after 24 to 48 days after grafting.

Regulation of Natural Killer Cell Activity and Interferon Production in the Rat Lung Following Aerosol Challenge

High levels of natural cytotoxicity were detected in vitro in cells from the lung interstitium of the rat following collagenase digestion of lung tissue. In contrast, alveolar cells exhibited negligible levels of natural cytotoxicity and furthermore suppressed the natural cytotoxicity of interstitial lung leukocytes. This suppression was alleviated following in vivo administration of indomethacin. The natural cytotoxicity of cells from both the lung and spleen was transiently suppressed following exposure of normal rats to aerosols of Escherichia coli lipopolysaccharide or of ovalbumin-sensitized rats to an ovalbumin aerosol. Parenchymal lung leukocytes, like those from the spleen and peripheral blood, showed enhanced cytotoxicity when treated with interferon in vitro. In addition interstitial leukocytes were capable of producing interferon when cocultured with P815 cells and, as was the case with the spleen, low density cells produced the most interferon. However, alveolar cells did not produce interferon in this system. These studies suggest that the lung is capable of self-regulation of the high levels of natural cytotoxicity present in interstitial tissue; alveolar cells or their products may suppress interstitial natural killer cells whilst interstitial leukocytes have the capacity to stimulate natural killer cells by producing interferon.

Indomethacin and Poly I:C in the Inhibition of Carcinogen-Induced Bladder Cancer in an Experimental Animal Model

Fischer rats, in whom superficial transitional cell cancers of the urinary bladder were induced by the carcinogen N-[4-(5-nitrofuryl)-2-thiazolyl] formamide, were inoculated intraperitoneally with either phosphate buffered saline, indomethacin (a prostaglandin synthetase inhibitor), poly I:C (an interferon inducer), or indomethacin together with poly I:C. While indomethacin alone appeared to have a significant albeit variable inhibitory effect on tumor size, poly I:C had a far more pronounced significant inhibitory effect. The combination of poly I:C and indomethacin together, however, led to the greatest inhibition in tumor growth, and in some instances, to tumor regression.Splenic lymphocytes from the same animals demonstrated enhanced natural cytotoxicity after treatment with poly I:C. Surprisingly, levels of natural cytotoxicity seen in animals treated with indomethacin and poly I:C together were lower than those seen with poly I:C alone. No enhancement of cytotoxicity could be demonstrated in vitro in lymphocytes from indomethacin-treated animals.Macrophages were also treated in this system under identical conditions. However, the activity of macrophages alone and of macrophages and lymphocytes together did not appear to be modified either by indomethacin alone or by the combination of prostaglandin synthetase inhibition and interferon induction together, the combination of which in vivo was suggested to be most effective in controlling tumor progression. Further studies to determine timing of these interactions and doses of immune response modifiers in order to characterize mechanisms possibly at work in modifying tumor growth in this system therefore seem highly indicated.