title: Multiple mechanisms of target cell disintegration are employed in cytotoxicity reactions mediated by human natural killer cells.
abstract: The rate of disintegration of target cells subsequent to lytic programming by human peripheral blood natural killer (NK) cells was investigated using a quantitative calcium pulse technique. The rate of this initial calcium-independent target cell disintegration was indicative of a first-order decay process for programmed target cells with a calculated half-life of less than 3 min. This initial, rapid disintegration phase was independent of the overall cytotoxic activity of the lymphocyte preparation tested. Moreover, initial rates of target cell disintegration were comparable for target cell lines that exhibit up to 6-fold differences in overall susceptibility to natural cytotoxicity. In these studies we also consistently observed very slow, calcium-independent disintegration of additional target cells following apparent completion of the rapid disintegration process. Using a 51Cr release assay and K-562 target cells, the kinetics of this slow disintegration process were examined and found to be similar for donors exhibiting up to a 2-fold difference in overall cytotoxic activity and independent of the concentration of programed target cells. Whereas the initial rapid disintegration mechanism was independent of temperature over the range of 10-37 degrees C, the slow disintegration mechanism exhibited a direct dependence on the incubation temperature. Furthermore, we observed that supernatants obtained after the termination of lytic programing by ethylene diaminetetraacetic acid could effect the slow lysis of fresh NK-susceptible target cell lines. These results support the utilization of at least two distinct mechanisms for target cell lysis by human NK cells.
authors.affiliation: Department of Chemistry, Oakland University, Rochester, Mich.
authors.forename: C L
authors.initials: CL
authors.lastname: Sevilla
authors.forename: G
authors.initials: G
authors.lastname: Radcliff
authors.forename: N H
authors.initials: NH
authors.lastname: Mahle
authors.forename: S
authors.initials: S
authors.lastname: Swartz
authors.forename: M D
authors.initials: MD
authors.lastname: Sevilla
authors.forename: J
authors.initials: J
authors.lastname: Chores
authors.forename: D M
authors.initials: DM
authors.lastname: Callewaert
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004578:Electron Spin Resonance Spectroscopy; D006461:Hemolysis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis; D008560:Membrane Fluidity; D008875:Middle Aged; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D002118:Calcium