Mechanism of chlorphentermine-induced lymphocyte toxicity: initial investigations

Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5386092

Sauers, L J; Wierda, D; Reasor, M J

Chlorphentermine (CP) inhibits the blastogenic response of mouse splenic and human peripheral blood lymphocytes to the T-cell mitogens, phytohemagglutinin (PHA) and concanavalin A (Con A). The purpose of these studies was to examine in vitro the mechanism mediating this immunosuppression. If mouse or human lymphocytes are pretreated with CP for 30 minutes, then stimulated with PHA, their blastogenic response is inhibited 80% and 45%, respectively. However, if CP is not added until 10 minutes or later following PHA stimulation, the inhibitory effect of the drug is essentially eliminated. The authors also determined that CP can potentiate Con A-induced agglutination of human lymphocytes. Enhanced agglutination can result from changes in the integrity of membrane phospholipids. Because changes in membrane phospholipid biochemistry characteristically occur within 10 minutes after mitogen-induced lymphocyte activation, the authors examined whether CP altered the incorporation of choline into cellular phospholipids. They found that CP decreases overall incorporation of /sup 14/C-choline into cellular phospholipids of mouse lymphocytes by 45% during the first 4 hours of activation. These data suggest that the immunotoxicity associated with CP may be mediated by drug-induced changes at the membrane level that appear to occur early during lymphocyte activation.

• Research Organization: West Virginia Univ. Medical Center, Morgantown
• OSTI ID: 5386092
• 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. 45:3; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AGGLUTININS
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
AMPHETAMINES
ANALEPTICS
ANIMAL CELLS
ANIMALS
ANTIBODIES
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM AGENTS
CHOLINE
CONCANAVALIN
CONNECTIVE TISSUE CELLS
DRUGS
ESTERS
HEMAGGLUTININS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LECTINS
LEUKOCYTES
LIPIDS
LIPOTROPIC FACTORS
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MICE
MITOGENS
MUCOPROTEINS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
PHYTOHEMAGGLUTININ
POLYSACCHARIDES
PRIMATES
PROTEINS
QUATERNARY COMPOUNDS
RODENTS
SACCHARIDES
SOMATIC CELLS
SPLEEN CELLS
SYMPATHOMIMETICS
TOXICITY
TRACER TECHNIQUES
VERTEBRATES