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Phorbol ester-induced proliferation of interleukin 2 (IL 2)-dependent murine T cells and inhibition by gangliosides

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6644468
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The authors have shown that gangliosides inhibit the growth of IL 2-dependent T cells. Phorbol myristate acetate (PMA) was tested as a proliferative stimulus in an effort to isolate a protein kinase C (PKC)-activated pathway in these cells as a potential target for ganglioside inhibition. CT-6 murine T cells were cultured at 5 x 10/sup 4/ cells/ml in the presence of PMA, IL 2, or both, and in the presence or absence of gangliosides. PMA (1-20 nM) stimulated CT-6 cell division in IL 2-free media, as measured by increases in /sup 3/H-thymidine uptake or by actual cell counts. Inactive tumor promotors were ineffective stimulators of CT-6 growth. in time course studies, PMA induction paralleled IL 2 induction of growth, but the mitogenic index of 25% IL 2-containing media was from 1.3 to 2.1 times that of PMA. IL 2 and PMA-induced proliferation were not synergistic; rather, PMA reduced IL 2-stimulated growth. Various purified gangliosides inhibited PMA-induced proliferation; the (I)/sub 50/ of each ganglioside was similar comparing PMA and IL 2-induced growth. In both cases, GM/sub 2/ was the most potent inhibitor and neutral glycolipids were ineffective. The results suggest that a PKC-dependent pathway is functional in IL 2-dependent T cells, that maximal proliferation requires other events unrelated to PKC activation, and that the PKC pathway is a primary target of ganglioside inhibition in these cells.
Research Organization:
George Washington Univ. School of Medicine and Health Sciences, Washington, DC
OSTI ID:
6644468
Report Number(s):
CONF-8606151-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CARCINOGENS
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERS
GANGLIOSIDES
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
LIPIDS
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MATERIALS
MICE
MITOGENS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
PYRIMIDINES
RIBOSIDES
RODENTS
SACCHARIDES
SOMATIC CELLS
THYMIDINE
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
VERTEBRATES