Tumor-activated NK cells trigger monocyte oxidative metabolism.
We have examined the hypothesis that tumor cells can stimulate a respiratory burst by human natural killer (NK) cells in vitro as measured by luminol-dependent chemiluminescence (CL). Percoll-purified NK cells, containing 40% HNK-1+ cells and less than 1 to 4% esterase-positive contaminating monocytes, can generate a strong CL response after stimulation with the NK-susceptible K562 tumor but not with the NK-resistant P815 tumor cells. Although the response was NK dependent, as shown by depletion with NK-directed monoclonal antibodies (HNK-1, OKT-11, and OKM-1), the cell generating the CL response was not the NK cell. On the basis of several independent experimental approaches the CL response always required the presence of monocytes in the NK preparation. a) Treatment with a monocyte-specific monoclonal antibody (MO2) and complement completely abolished CL. b) The cells producing the CL response were strongly adherent to nylon wool columns (NWC), and large granular lymphocyte preparations containing less than 0.1% esterase-positive cells were inactive. c) NK cells cultured in IL 2-containing medium and tested over several days did not generate CL. d) Optimal numbers of monocytes (less than 1 to 2%) added to a non-CL NWC-purified NK population restored CL, whereas larger or smaller amounts were ineffective. Neither these procedures nor the addition of superoxide dismutase (which completely blocked CL) had any effect on NK lytic activity. We subsequently demonstrated that a factor present in supernatants obtained from NK/K562 incubations, but not from NK or tumor cells alone, could stimulate monocyte CL. We therefore propose that the CL response measured in NK-enriched Percoll fractions originated from contaminating monocytes that were triggered by factor(s) released from tumor-activated NK cells, and that superoxide anion was not required for NK lysis.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D002448:Cell Adhesion; D002450:Cell Communication; D002469:Cell Separation; D002499:Centrifugation, Density Gradient; D003470:Culture Media; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D055646:Killer Factors, Yeast; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology; D008163:Luminescent Measurements; D008213:Lymphocyte Activation; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011506:Proteins / Q000502:physiology
D000911:Antibodies, Monoclonal; D003470:Culture Media; D055646:Killer Factors, Yeast; D010835:Phytohemagglutinins; D011506:Proteins