Stimulus-specific induction of phospholipid and arachidonic acid metabolism in human neutrophils

Journal Article · Wed Apr 01 00:00:00 EST 1987 · J. Cell Biol.; (United States)

DOI:https://doi.org/10.1083/jcb.104.4.925· OSTI ID:6793284

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

Phospholipid remodeling resulting in arachidonic acid (AA) release and metabolism in human neutrophils stimulated by calcium ionophore A23187 has been extensively studied, while data obtained using physiologically relevant stimuli is limited. Opsonized zymosan and immune complexes induced stimulus-specific alterations in lipid metabolism that were different from those induced by A23187. (/sup 3/H)AA release correlated with activation of phospholipase A2 (PLA2) but not with cellular activation as indicated by superoxide generation. The latter correlated more with calcium-dependent phospholipase C (PLC) activation and elevation of cellular diacylglycerol (DAG) levels. When cells that had been allowed to incorporate (/sup 3/H)AA were stimulated with A23187, large amounts of labeled AA was released, most of which was metabolized to 5-HETE and leukotriene B4. Stimulation with immune complexes also resulted in the release of (/sup 3/H)AA but this released radiolabeled AA was not metabolized. In contrast, stimulation with opsonized zymosan induced no detectable release of (/sup 3/H)AA. Analysis of (/sup 3/H)AA-labeled lipids in resting cells indicated that the greatest amount of label was incorporated into the phosphatidylinositol (PI) pool, followed closely by phosphatidylcholine and phosphatidylserine, while little (/sup 3/H)AA was detected in the phosphatidylethanolamine pool. During stimulation with A23187, a significant decrease in labeled PI occurred and labeled free fatty acid in the pellet increased. With immune complexes, only a small decrease was seen in labeled PI while the free fatty acid in the pellets was unchanged. In contrast, opsonized zymosan decreased labeled PI, and increased labeled DAG. Phospholipase activity in homogenates from human neutrophils was also assayed. A23187 and immune complexes, but not zymosan, significantly enhanced PLA2 activity in the cell homogenates. On the other hand, PLC activity was enhanced by zymosan and immune complexes. (Abstract Truncated)

• Research Organization: Smith Kline and French Laboratories, Swedeland, PA
• OSTI ID: 6793284
• Journal Information: J. Cell Biol.; (United States), Vol. 4
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ARACHIDONIC ACID
BIOCHEMICAL REACTION KINETICS
NEUTROPHILS
METABOLISM
PHOSPHOLIPIDS
CALCIUM
ENZYME ACTIVITY
IN VITRO
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALINE EARTH METALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
ELEMENTS
ESTERS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LEUKOCYTES
LIPIDS
MATERIALS
METALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
REACTION KINETICS
550201* - Biochemistry- Tracer Techniques