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Induction of cytosolic phospholipase A2 activity by phosphatidic acid and diglycerides in permeabilized human neutrophils: interrelationship between phospholipases D and A2.

Abstract
Relationships between phospholipases are poorly understood, but phosphatidic acid (PA) and diglycerides (DGs), produced by phospholipase D (PLD) and phosphatidate phosphohydrolase actions, might function as second messengers coupling cell stimulation to cellular responses. This study investigates the role of PLD-mediated PA and DG formation in inducing phospholipase A2 (PLA2) activity in intact human neutrophils (PMNs) and in PMNs permeabilized with Staphylococcus aureus alpha-toxin. PMNs were labelled with [3H]arachidonic acid (AA) to assess AA release and metabolism and diacylglycerol formation, or with [3H]1-O-hexadecyl-2-lyso-glycerophosphatidylcholine for the determination of platelet-activating factor (PAF), PA and alkylacylglycerol production. In intact PMNs primed with tumour necrosis factor alpha before stimulation with N-formyl-Met-Leu-Phe, AA release and metabolism and PAF formation increased in parallel with enhanced PA and DG formation, and inhibition of PA and DG production led to a decrease in both AA release and PAF accumulation. In alpha-toxin-permeabilized PMNs, AA release and PAF production result from the specific activation of cytosolic PLA2 (cPLA2). In this system, PA and DG formation were always present when cPLA2 activation occurred; blocking PA and DG production inhibited AA release and PAF accumulation. Adding either PA or DG back to permeabilized cells (with endogenous PA and DG formation blocked) led to a partial restoration of AA release and PAF formation; a combination of PA and DGs reconstituted full cPLA2 activity. These results strongly suggest that products of PLD participate in activating cPLA2 in PMNs.
AuthorsS A Bauldry, R E Wooten
JournalThe Biochemical journal (Biochem J) Vol. 322 ( Pt 2) Pg. 353-63 (Mar 01 1997) ISSN: 0264-6021 [Print] England
PMID9065750 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Bacterial Toxins
  • Diglycerides
  • Hemolysin Proteins
  • Phosphatidic Acids
  • Platelet Activating Factor
  • Tumor Necrosis Factor-alpha
  • staphylococcal alpha-toxin
  • Arachidonic Acid
  • Ethanol
  • N-Formylmethionine Leucyl-Phenylalanine
  • Phospholipases A
  • Phospholipases A2
  • Phospholipase D
Topics
  • Arachidonic Acid (metabolism)
  • Bacterial Toxins (pharmacology)
  • Cell Membrane Permeability
  • Cytosol (enzymology)
  • Diglycerides (biosynthesis, pharmacology)
  • Dose-Response Relationship, Drug
  • Enzyme Induction
  • Ethanol (pharmacology)
  • Hemolysin Proteins (pharmacology)
  • Humans
  • N-Formylmethionine Leucyl-Phenylalanine (pharmacology)
  • Neutrophils (drug effects, enzymology)
  • Phosphatidic Acids (biosynthesis, pharmacology)
  • Phospholipase D (metabolism)
  • Phospholipases A (biosynthesis)
  • Phospholipases A2
  • Platelet Activating Factor (metabolism)
  • Tumor Necrosis Factor-alpha (pharmacology)

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