Cells of the J774 macrophage cell line are primed for antibody-dependent cell-mediated cytotoxicity following exposure to. gamma. -irradiation

Journal Article · Sun Sep 01 00:00:00 EDT 1991 · Cellular Immunology; (United States)

DOI:https://doi.org/10.1016/0008-8749(91)90359-J· OSTI ID:5160087

Duerst, R; Werberig, K ^[1]

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1. University of Rochester Medical Center, New York (USA)

Activation of macrophages (M phi) for host defense against tumor cells follows a sequence of priming events followed by an initiating stimulus that results in production and release of cytotoxic molecules that mediate target cell killing. The authors have developed a model to study specific macrophage cytotoxicity in vitro utilizing a cultured murine M phi cell line, J774. Specific cytotoxicity of cultured human gastrointestinal tumor cells is achieved in the presence of murine IgG2a monoclonal antibody (mAb) 17-1-A. The ability of these cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) is greatly enhanced following gamma-irradiation. ADCC can be demonstrated at mAb 17-1-A concentrations greater than or equal to 1 microgram/ml and effector/target cell ratios greater than or equal to 2. Exposure to doses greater than or equal to 10 Gy of gamma-irradiation increases ADCC threefold. Varying the duration from J774 M phi exposure to {gamma}-irradiation until addition of antibody-coated target cells showed that the primed state for ADCC is stable for at least 8 days but approximately 24 hr is required for complete development of the primed state. mAb-dependent target cell death begins 8 hr after addition of mAb and labeled target cells to primed effector cells and is complete by 24 hr. Incubation of unirradiated J774 M phi effector cells with recombinant murine interferon-{gamma} (rmIFN-{gamma}) also results in enhanced ADCC, but the extent of target cell killing achieved is less than that following priming by {gamma}-irradiation. Concomitant priming of {gamma}-irradiated J774 M phi with rmIFN-{gamma} increases the extent of ADCC. Further study of irradiated J774 cells may elucidate the molecular pathways utilized by M phi for achieving and maintaining the primed state for ADCC.

• OSTI ID: 5160087
• Journal Information: Cellular Immunology; (United States), Vol. 136:2; ISSN 0008-8749
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
INTERFERON
RADIOSENSITIVITY EFFECTS
MACROPHAGES
BIOLOGICAL FUNCTIONS
TUMOR CELLS
CELL KILLING
DOSE-RESPONSE RELATIONSHIPS
GAMMA RADIATION
GASTROINTESTINAL TRACT
IN VITRO
MICE
MONOCLONAL ANTIBODIES
ANIMAL CELLS
ANIMALS
ANTIBODIES
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
ELECTROMAGNETIC RADIATION
GROWTH FACTORS
IONIZING RADIATIONS
LYMPHOKINES
MAMMALS
MITOGENS
ORGANIC COMPOUNDS
PHAGOCYTES
PROTEINS
RADIATIONS
RODENTS
SOMATIC CELLS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture