Menadione modifies superoxide anion (O/sub 2/) generation in human neutrophils and HL-60 cells
Menadione, a derivative of the natural vitamins K, has antineoplastic and antiinflammatory properties. Its profound biochemical effects upon resting and stimulated neutrophils make these cells a likely target of its purported therapeutic actions. They found superoxide dismutase-inhibitable O/sub 2/ production, a major mechanism of leukocyte-mediated cell damage, to be enhanced in resting neutrophils by menadione, as a function of cell number, time and concentration. Conversely, in phorbol myristate acetate (PMA)-stimulated neutrophils, menadione significantly reduced the rate and magnitude of O/sub 2/ generation. The release of O/sub 2/ induced by formylated peptide (fmlp) and calcium ionophore A23187, as well as PMA were inhibited in a concentration dependent manner by menadione. Furthermore, inhibition was enhanced by incubation of resting neutrophils with menadione for 30 min prior to addition of stimulants. Also examined were the effects of menadione on human promyelocytic leukemia(HL-60) cells induced into granulocytic differentiation with dimethylsulfoxide. As in human neutrophils, menadione stimulated O/sub 2/ release in resting HL-60 cells and inhibited this response in PMA-treated cells, indicating the HL-60 cell line as suitable for the study of menadione's actions. Future experiments will elucidate the nature and loci of interaction of menadione with neutrophil activation mechanisms.
- Research Organization:
- Medical College of Virginia, Richmond
- OSTI ID:
- 6897010
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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
ANTINEOPLASTIC DRUGS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
COAGULANTS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
ESTERS
HEMATOLOGIC AGENTS
HEMIC DISEASES
HEPARIN ANTAGONISTS
KINETICS
LEUKEMIA
LEUKOCYTES
MAMMALS
MAN
MATERIALS
NEOPLASMS
NEUTROPHILS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
PHORBOL ESTERS
PRIMATES
QUINONES
RADICALS
REACTION KINETICS
SUPEROXIDE DISMUTASE
SUPEROXIDE RADICALS
SYNTHESIS
TIME DEPENDENCE
TUMOR CELLS
VERTEBRATES
VITAMIN K
VITAMINS