Role of oxygen-dependent mechanisms in monoclonal antibody-induced lysis of normal T cells by phagocytes. I.--Human Phagocytes. 1985

R M Golub, and B Descamps-Latscha

The present study investigates the lytic potential of the reactive oxygen species (ROS) which, as previously shown in our laboratory, are generated within the first minutes following the Fc-receptor-mediated interaction between phagocytic cells and anti-T-cell monoclonal-antibody (mAb)-coated T lymphocytes. A comparative study of ROS production (measured by chemiluminescence (CL] and the cytotoxic effect (evaluated in a 51Cr release antibody-dependent cellular cytotoxicity (ADCC) assay) of human polymorphonuclear (PMN) and mononuclear (MN) cells against mAb-coated autologous, allogeneic and xenogeneic (murine) thymocytes showed that the two reactions were closely interdependent for PMN and co-existed without significant correlation for MN cells. Catalase and superoxide dismutase did not modify ADCC results, suggesting that these ROS scavengers could not diffuse into the target cell destruction area. Colchicine treatment of PMN and MN cells at a dose inhibiting phagocytosis consistently impaired their CL generation and, in parallel, strongly reduced PMN-mediated ADCC but only weakly reduced that of MN cells. PMN and MN cells from 14 patients with chronic granulomatous disease (CGD) were not capable of producing CL after contact with mAb-coated T cells and showed significantly reduced ADCC activities, while PMN and MN cells from mothers carrying the X-linked type of CGD exhibited ADCC and oxidative responses of an intermediate level. We conclude that ADCC mediated by human PMN cells against T cells is mainly dependent upon the generation of ROS, whereas that induced by MN cells is most likely effected by both oxidative and non-oxidative events.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D010586 Phagocytes Cells that can carry out the process of PHAGOCYTOSIS. Phagocyte,Phagocytic Cell,Phagocytic Cells,Cell, Phagocytic,Cells, Phagocytic
D006105 Granulomatous Disease, Chronic A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern. Autosomal Recessive Chronic Granulomatous Disease,Chronic Granulomatous Disease,Chronic Granulomatous Disease, Atypical,Chronic Granulomatous Disease, X-Linked,Cytochrome B-Negative Granulomatous Disease, Chronic, X-Linked,Cytochrome B-Positive Granulomatous Disease, Chronic, X-Linked,Granulomatous Disease, Chronic, X-Linked,Granulomatous Disease, Chronic, X-Linked, Variant,X-Linked Chronic Granulomatous Disease,Chronic Granulomatous Disease, X Linked,Chronic Granulomatous Diseases,Granulomatous Diseases, Chronic,X Linked Chronic Granulomatous Disease
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000332 Aerobiosis Life or metabolic reactions occurring in an environment containing oxygen. Aerobioses
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000920 Antibody-Dependent Cell Cytotoxicity The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. ADCC,Cytotoxicity, Antibody-Dependent Cell,Cell Cytoxicity, Antibody-Dependent,Antibody Dependent Cell Cytotoxicity,Antibody-Dependent Cell Cytotoxicities,Antibody-Dependent Cell Cytoxicities,Antibody-Dependent Cell Cytoxicity,Cell Cytotoxicities, Antibody-Dependent,Cell Cytotoxicity, Antibody-Dependent,Cell Cytoxicities, Antibody-Dependent,Cell Cytoxicity, Antibody Dependent,Cytotoxicities, Antibody-Dependent Cell,Cytotoxicity, Antibody Dependent Cell,Cytoxicities, Antibody-Dependent Cell,Cytoxicity, Antibody-Dependent Cell

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