Inhibition of macrophage DNA synthesis by immunomodulators. II. Characterization of the suppression by muramyl dipeptide or lipopolysaccharide (/sup 3/H)thymidine incorporation into macrophages

Journal Article · Sat Dec 01 00:00:00 EST 1984 · Cell. Immunol.; (United States)

DOI:https://doi.org/10.1016/0008-8749(84)90344-7· OSTI ID:5977263

Nagao, S; Ikegami, S; Tanaka, A

Guinea pig peritoneal exudate macrophages actively incorporated (/sup 3/H)thymidine into trichloroacetic acid-insoluble fraction in vitro. The incorporation of (/sup 3/H)thymidine was almost completely inhibited by aphidicolin, an inhibitor of DNA polymerase alpha and an autoradiograph showed heavy labeling in nuclei of 15% of macrophage populations. These results indicate that the observed thymidine incorporation was due to a nuclear DNA synthesis. The (/sup 3/H)thymidine incorporation was markedly suppressed when macrophages were activated by immunoadjuvants such as muramyl dipeptide (MDP) or bacterial lipopolysaccharide (LPS). The suppression of (/sup 3/H)thymidine incorporation by MDP was neither due to the decrease in thymidine transport through the cell membrane, nor due to dilution by newly synthesized cold thymidine. An autoradiograph revealed that MDP markedly decreased the number of macrophages the nuclei of which were labeled by (/sup 3/H)thymidine. These results suggest that the suppression of (/sup 3/H)thymidine incorporation by the immunoadjuvants reflects a true inhibition of DNA synthesis. The inhibition of DNA synthesis by MDP was also observed in vivo. Further, it was strongly suggested that the inhibition was not caused by some mediators, such as prostaglandin E2, released from macrophages stimulated by the immunoadjuvants but caused by a direct triggering of the adjuvants at least at the early stage of activation. Cyclic AMP appears to be involved in the inhibitory reaction.

• Research Organization: Shimane Medical Univ., Izumo, Japan
• OSTI ID: 5977263
• Journal Information: Cell. Immunol.; (United States), Vol. 89:2
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
DNA REPLICATION
INHIBITION
MACROPHAGES
TERPENES
BIOLOGICAL EFFECTS
TRITIUM COMPOUNDS
UPTAKE
ACETIC ACID
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
CELL MEMBRANES
CELL NUCLEI
CHLORINE COMPOUNDS
DNA
ENZYME INHIBITORS
GUINEA PIGS
IN VITRO
LABELLING
LIPOPOLYSACCHARIDES
PEPTIDES
POLYMERASES
PROSTAGLANDINS
THYMIDINE
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
AZINES
CARBOHYDRATES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
ENZYMES
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MEMBRANES
MONOCARBOXYLIC ACIDS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
NUCLEOTIDYLTRANSFERASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHAGOCYTES
PHOSPHORUS-GROUP TRANSFERASES
POLYSACCHARIDES
PROTEINS
PYRIMIDINES
REACTION KINETICS
RIBOSIDES
RODENTS
SACCHARIDES
SOMATIC CELLS
TRANSFERASES
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550201 - Biochemistry- Tracer Techniques