Biomedical subjects
Publications and source records attributed to L Simchowitz.
The effector cell in abtibody-dependent lymphocyte-mediated cytotoxicity (ADLMC) have been studied. The cells do not adhere to glass and bear Fc receptors independent of surface Ig and complement receptors. Whereas monocytes have IgG1 and Ig G3 Fc receptors, these Fc receptor lymphocytes appear to have receptors for aggregates of all four IgG subclasses.
Isolated normal human peripheral neutrophils became cytotoxic to chicken red blood cells (CRBC) in the presence of phytohaemagglutinin (PHA) and concanavalin A (Con A), a phenomenon which we have termed lectin-dependent neutrophilmediated cytotoxicity (LDNMC). Substantial cytotoxicity could be demonstrated by 1 h of incubation at 37 degrees. Isolated human peripheral lymphocytes were not cytotoxic to CRBC in the presence of these lectins, even after 18 h of incubation. Both PHA and Con A exhibited dose responses over a wide concentration range and displayed progressive, time-dependent cytotoxicity. Cytotoxicity for both PHA and Con A was greater at 37 degrees than at 22 degrees, and was undetectable at 4 degrees. CRBC as target cells were much more readily lysed than either sheep or human erythrocytes. Erythrophagocytosis did not appear to play a role.
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.