Lectin-dependent neutrophil-mediated cytotoxicity. II. Possible mechanisms.
The mechanisms whereby neutrophils become cytotoxic to chicken erythrocyte (CRBC) target cells were investigated in a system of lectin-dependent neutrophil-mediated cytotoxicity (LDNMC). Through the use of drugs and specific metabolic inhibitors, LDNMC was found to be dependent on energy supplied by anaerobic glycolysis and on other active metabolic functions of the neutrophil. 2-Iodoacetamide, 2-deoxy-D-glucose, di-isopropyl-fluorophosphate, colchicine, cytochalasin B, and dibutyryl cyclic AMP all caused dose-dependent inhibition of cytotoxicity, while inhibitors of protein and nucleic acid synthesis were without effect. Cell surface membrane-active agents, such as chloroquine, hydrocortisone and chlorpromazine inhibited cytotoxicity, while vitamin A caused enhancement. Lectins which agglutinated neutrophils, but not necessarily CRBC, such as phytohaemagglutinin (PHA-P), concanavalin A (Con A), soybean agglutinin (SBA), and Ricinus communis agglutinin (RCA), mediated cytotoxicity while lectins which did not cause agglutination, such as pokeweed mitogen (PWM), did not mediate cytotoxicity. Preincubation of neutrophils, but not CRBC with PHA-P, resulted in time-dependent enhancement of cytotoxicity, while pre-incubation with Con A yielded progressive inhibition of cytotoxicity. These studies suggest that lectin binding to the cell surface causes alterations of the membrane, that LDNMC requires cell to cell surface contact, and that cytotoxicity depends on active metabolic processes.
D000963:Antimetabolites / Q000494:pharmacology; D002462:Cell Membrane; D003601:Cytotoxicity Tests, Immunologic; D004912:Erythrocytes / Q000276:immunology; D006019:Glycolysis; D006801:Humans; D007460:Iodoacetamide / Q000494:pharmacology; D037102:Lectins / Q000494:pharmacology; D008358:Mannose / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D010085:Oxidative Phosphorylation
D000963:Antimetabolites; D037102:Lectins; D008358:Mannose; D007460:Iodoacetamide