Phorbal esters and calcium ionophore can prime murine peritoneal macrophages for tumor cell destruction

Journal Article · Sun Jun 01 04:00:00 EDT 1986 · J. Immunol.; (United States)

OSTI ID:5458110

Somers, S D; Weiel, J E; Hamilton, T A; Adams, D O

Murine macrophages from sites of inflammation develop toward tumoricidal competence by exposure to a macrophage-activating factor such as interferon-..gamma.. (IFN-..gamma..). To explore the biochemical transductional events initiated by IFN-..gamma.., peritoneal macrophages from C57BL/6J mice elicited by various sterile irritants were treated in vitro with two pharmacologic agents that mimic the action of certain second messengers. Phorbol myristate acetate (PMA) and the ionophore A23187 cooperatively reproduced the ability of IFN-..gamma.. to prime macrophages for tumoricidal function. Neither agent alone was able to prime macrophages. The two agents acted on the macrophages, and target susceptibility to kill was not altered by PMA and A23187. Only active phorbol esters, which are known to bind and stimulate protein kinase C, were able to cooperate with A23187 to induce priming. A cell-permeable synthetic diacylglycerol (sn-1,2-dioctanoyl glycerol) could also prime for cytolysis. In the presence of PMA, A23187, and EGTA, addition of Ca/sup + +/ was sufficient for priming, whereas the addition of Mg/sup + +/ was much less efficient. Priming by IFN-..gamma.., however, was not blocked by EGTA. Efflux of /sup 45/Ca/sup + +/ from preloaded cells was significantly increased by A23187 and by IFN-..gamma... Quin-2/AM, an intracellular chelator of Ca/sup + +/, blocked priming by IFN-..gamma...

• Research Organization: Duke Univ. Medical Center, Durham, NC
• OSTI ID: 5458110
• Journal Information: J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 136:11; ISSN JOIMA
• Country of Publication: United States
• Language: English

Related Subjects

551001 -- Physiological Systems-- Tracer Techniques
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CARCINOGENS
CATIONS
CELL KILLING
CHARGED PARTICLES
CHELATING AGENTS
CHEMICAL ACTIVATION
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
ESTERS
EVEN-ODD NUCLEI
GROWTH FACTORS
INFLAMMATION
INTERFERON
INTERMEDIATE MASS NUCLEI
IONS
ISOTOPE APPLICATIONS
ISOTOPES
LYMPHOKINES
MACROPHAGES
MAGNESIUM COMPOUNDS
MAMMALS
MICE
MITOGENS
NUCLEI
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PHAGOCYTES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
RADIOISOTOPES
RODENTS
SOMATIC CELLS
SYMPTOMS
TRACER TECHNIQUES
TRANSFERASES
TUMOR CELLS
VERTEBRATES