Activation of phospholipase C in human neutrophils (PMN) by phorbol myristate acetate (PMA)

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6846577

Agwu, D E; McPhail, L C; Daniel, L W; Bass, D A; McCall, C E

PMA is a potent agonist for human PMN. Prior exposure of PMN to PMA can either enhance or inhibit responses to a second stimulus. Diglyceride (DG) and phosphatidic acid (PA) can modulate cell functions and, with protein kinase C(PKC), could aid in PMA-induced effects on PMN. Since PMA does not induce polyphosphoinositide turnover, they investigated the effect of PMA on the metabolism of a more prevalent phospholipid, 1-0-alkyl-2-acyl-sn-glycerophosphocholine(alkyl PC). PMN were incubated with 1-0-(/sup 3/H)-hexadecyl-2-lyso-sn-glycerophosphocholine and approx. 85% of the label incorporated into alkyl PC. Stimulation by 1.6 ..mu..M PMA induced rapid (< 1 min) breakdown of alkyl PC into both alkyl DG and PA. Production of DG and PA was maximal at 15 min and 5 min, respectively. At 20 min, the amount of DG and PA increased from 0.8 +/- 0.5 to 7.6 +/- 2.3 and from 0.5 +/- 0.1 to 5.2 +/- 1.1, respectively (percent of total label, mean +/- SD, n=4). Production of DG and PA was dose-dependent, reaching maximum at 16 nM. Synthetic alkyl DG was tested for possible effects on PKC. At 10 ..mu..g/ml, alkyl DG did not activate PKC in PMN cytosolic preparations. However, alkyl DG inhibited activation by diolein or oleoyl-acetyl-glycerol. Thus, PMA may induce activation of an alkyl PC phospholipase C. The alkyl DG formed could modulate PKC activity and mediate feedback inhibitory effects of PMA on PMN and other cells.

• Research Organization: Wake Forest Univ. Medical Center, Winston-Salem, NC
• OSTI ID: 6846577
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLESTERASES
CARCINOGENS
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
ESTERASES
ESTERS
HYDROLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
LIPASE
LIPIDS
MAMMALS
MAN
MATERIALS
METABOLISM
NEUTROPHILS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHORBOL ESTERS
PHOSPHOLIPIDS
PRIMATES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES