Mechanisms of antibody-dependent cellular cytotoxicity. The use of effector cells from chronic granulomatous disease patients as investigative probes

P. Katz, C. B. Simone, P. A. Henkart, A. Fauci

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalJournal of Clinical Investigation
Volume65
Issue number1
StatePublished - Jan 1 1980
Externally publishedYes

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Chronic Granulomatous Disease
Antibodies
Monocytes
Neutrophils
Suspensions
Lymphocytes
Leukocytes
Cytophagocytosis
Respiratory Burst
Colchicine
Phagocytes
Phagocytosis
Superoxides
Hydrogen Peroxide
Erythrocytes

ASJC Scopus subject areas

  • Medicine(all)

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Mechanisms of antibody-dependent cellular cytotoxicity. The use of effector cells from chronic granulomatous disease patients as investigative probes. / Katz, P.; Simone, C. B.; Henkart, P. A.; Fauci, A.

In: Journal of Clinical Investigation, Vol. 65, No. 1, 01.01.1980, p. 55-63.

Research output: Contribution to journalArticle

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