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 04:00:00 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), Journal Name: Cell. Immunol.; (United States) Vol. 89:2; ISSN CLIMB
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- 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.
ACETIC ACID
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
AZINES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARBOHYDRATES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CELL NUCLEI
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
DNA
DNA REPLICATION
ENZYME INHIBITORS
ENZYMES
GUINEA PIGS
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
IN VITRO
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LABELLING
LIPIDS
LIPOPOLYSACCHARIDES
MACROPHAGES
MAMMALS
MEMBRANES
MONOCARBOXYLIC ACIDS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
NUCLEOTIDYLTRANSFERASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
PHAGOCYTES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
POLYSACCHARIDES
PROSTAGLANDINS
PROTEINS
PYRIMIDINES
REACTION KINETICS
RIBOSIDES
RODENTS
SACCHARIDES
SOMATIC CELLS
TERPENES
THYMIDINE
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES