Phospholipid metabolism in zymosan stimulated human monocytes: modulation by cyclic AMP (cAMP)

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7170686

Godfrey, R W; Manzi, R M; Hoffstein, S T

Oxygenated products of arachidonic acid (AA) are critical components in the development of the inflammatory response. Monocytes exposed to inflammatory stimuli are capable of converting free AA into these bioactive molecules. However, the limiting step in the formation of these compounds is thought to be the mechanism responsible for the release of esterified AA from phospholipids. When (/sup 3/H) AA labeled monocytes were challenged with opsonized zymosan, 28 +/- 2% of the incorporated counts were released compared to 8 +/- 1% for the control. Upon pretreatment with isobutyl methyl xanthine (IBMX) or dibutyrl cyclic AMP (d-cAMP) zymosan stimulated AA release was markedly reduced. The IC/sub 50/'s were 4 x 10/sup -4/M and 7 x 10/sup -4/M respectively. Analysis of (/sup 3/H) AA incorporation into cellular phospholipids showed that phosphatidylcholine (PC) and phosphatidylinositol (PI) were the primary pools labeled. Loss of label from both of these pools was evident after exposure to zymosan, however, pretreatment of cells with IBMX or d-cAMP inhibited release of (/sup 3/H)AA from the PC pool but not from the PI pool. The results show that human monocytes challenged with opsonized zymosan release arachidonic acid via cAMP-dependent and independent pathways. Furthermore, they suggest that a phospholipase activity (possibly A/sub 2/) against PC is modulated by cAMP.

• Research Organization: Smith Kline and French Labs., Philadelphia, PA
• OSTI ID: 7170686
• 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

Related Subjects

550501* -- Metabolism-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMP
ANIMALS
ARACHIDONIC ACID
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
ENZYMES
ESTERASES
ESTERS
HYDROLASES
INFLAMMATION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
LIPASE
LIPIDS
MAMMALS
MAN
MATERIALS
METABOLISM
MONOCARBOXYLIC ACIDS
MONOCYTES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PATHOLOGICAL CHANGES
PHOSPHOLIPIDS
PRIMATES
SECRETION
SYMPTOMS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
ZYMOSAN