TY - JOUR
T1 - Mechanisms of antibody-dependent cellular cytotoxicity. The use of effector cells from chronic granulomatous disease patients as investigative probes
AU - Katz, P.
AU - Simone, C. B.
AU - Henkart, P. A.
AU - Fauci, A.
PY - 1980
Y1 - 1980
N2 - The present study characterized the antibody-dependent cellular cytoxicity (ADCC) of leukocyte effector cells (neutrophils, lymphocytes, and monocytes) from normal subjects and from chronic granulomatous disease (CGD) patients. CGD phagocytic cells (neutrophils and monocytes) had depressed ADCC activity against antibody-coated human erythrocyte (HRBC) targets in suspension cultures indicative of abnormal intracellular postphagocytic killing. However, when phagocytosis was prevented by using a monolayer of antibody-coated HRBC targets, CGD monocytes, neutrophils, and lymphocytes exhibited normal ADCC activity. Similarly, antibody-coated HRBC targets in suspension could be lysed normally by CGD effector cells when phagocytosis was inhibited by the addition of in vitro colchicine. Extracellular lysis of autologous antibody-coated lymphoid cell targets in suspension was mediated normally by CGD effector cells. Thus, standard ADCC against HRBC targets in suspension is predominantly indicative of postphagocytic killing and, as such, is dependent upon a normal postphagocytic respiratory burst of oxidative metabolism which is deficient in CGD neutrophils and monocytes. Extracellular killing of sensitized targets does not appear to be dependent upon the generation of hydrogen peroxide (H2O2) and/or superoxide (O2-) and is normal in CGD neutrophils and monocytes. Hence, by employing CGD leukocytes as investigative probes in ADCC, fundamental mechanisms of intracellular vs. extracellular expression of cytotoxicity have been delineated.
AB - The present study characterized the antibody-dependent cellular cytoxicity (ADCC) of leukocyte effector cells (neutrophils, lymphocytes, and monocytes) from normal subjects and from chronic granulomatous disease (CGD) patients. CGD phagocytic cells (neutrophils and monocytes) had depressed ADCC activity against antibody-coated human erythrocyte (HRBC) targets in suspension cultures indicative of abnormal intracellular postphagocytic killing. However, when phagocytosis was prevented by using a monolayer of antibody-coated HRBC targets, CGD monocytes, neutrophils, and lymphocytes exhibited normal ADCC activity. Similarly, antibody-coated HRBC targets in suspension could be lysed normally by CGD effector cells when phagocytosis was inhibited by the addition of in vitro colchicine. Extracellular lysis of autologous antibody-coated lymphoid cell targets in suspension was mediated normally by CGD effector cells. Thus, standard ADCC against HRBC targets in suspension is predominantly indicative of postphagocytic killing and, as such, is dependent upon a normal postphagocytic respiratory burst of oxidative metabolism which is deficient in CGD neutrophils and monocytes. Extracellular killing of sensitized targets does not appear to be dependent upon the generation of hydrogen peroxide (H2O2) and/or superoxide (O2-) and is normal in CGD neutrophils and monocytes. Hence, by employing CGD leukocytes as investigative probes in ADCC, fundamental mechanisms of intracellular vs. extracellular expression of cytotoxicity have been delineated.
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U2 - 10.1172/JCI109660
DO - 10.1172/JCI109660
M3 - Article
C2 - 6243141
AN - SCOPUS:0018916976
VL - 65
SP - 55
EP - 63
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 1
ER -