Polymorphonuclear leukocyte-mediated, antibody-dependent, cellular cytotoxicity against tumor cells: dependence on oxygen and the respiratory burst.
Experiments were done to determine 1) whether the respiratory burst of superoxide anion (O2-) production in polymorphonuclear leukocytes (PMN) is triggered during antibody-dependent killing of tumor cells and 2) whether O2- production is essential for cytotoxicity. Three parameters of the respiratory burst (1-14C-glucose oxidation, oxygen consumption, and O2- release) were increased 2.5- to 7.3-fold during killing of antibody-primed tumor cells by human PMN. Added catalase and superoxide dismutase did not inhibit lysis, possibly because these enzymes were unable to diffuse into the inter-plasma-membrane space between killer and target cells. Evidence for an O2- requirement for cytotoxicity was the fact that concentrations of amobarbital or phenylbutazone sufficient to inhibit the cyanide-insensitive respiration of PMN also inhibited cytotoxicity. Also, hypoxic conditions inhibited cytotoxicity from 29 to 73%. The requirement for oxygen was most likely related to O2- generation and not mitochondrial respiration since cyanide and azide, which inhibit mitochondrial respiration, increased cytotoxicity.
D000230:Adenocarcinoma / Q000276:immunology*; D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000276:immunology; D007700:Kinetics; D009249:NADP / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010101:Oxygen Consumption; D010586:Phagocytes / Q000276:immunology; D010653:Phenylbutazone / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D009249:NADP; D010653:Phenylbutazone; D000654:Amobarbital; D005947:Glucose