Bacterial phosphatidylcholine-preferring phospholipase c reversibly inhibits the membrane component of the NADPH oxidase in human polymorphonuclear leukocytes: Implications for host defense

Ann E. Traynor*, Sigmund A. Weitzman, Leo I. Gordon

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Bacterial phosphatidylcholine-preferring phospholipase C (PC-PLC) has been recognized as a virulence factor and is implicated in the hemolytic and dermonecrotic properties associated with certain organisms. Moreover, recent data suggest that PC-PLC may be an important component in the signal transduction cascade by contributing to diacylglycerol (DAG) mass via the hydrolysis of phosphatidylcholine (PC). We have previously shown that PC-PLC can inhibit superoxide generation in human polymorphonuclear leukocytes (PMN). We now extend these observations and show that the mechanism of PC-PLC inhibition of superoxide generation is reversible inhibition of the membrane component of the NADPH oxidase (in a cell-free system) accompanied by expected generation of DAG and phosporylcholine. Addition of PC reversed the effects of the enzyme. Surprisingly, we also found that phosphatidic acid (PA), the hydrolysis product of phospholipase D, was also produced in intact PMN following PC-PLC exposure. Subsequent addition of the agonist N -formylmethionyl-phenylalanine resulted in further PA production. Restoration of PA in cell-free preparations partially restored superoxide generating capability. We conclude that PC-PLC may enhance bacterial virulence by inhibiting superoxide generation by human PMN, and that this effect is due to direct inhibition of the membrane component of the NADPH oxidase.

Original languageEnglish (US)
Pages (from-to)582-593
Number of pages12
JournalCellular Immunology
Volume152
Issue number2
DOIs
StatePublished - Dec 1993

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Bacterial phosphatidylcholine-preferring phospholipase c reversibly inhibits the membrane component of the NADPH oxidase in human polymorphonuclear leukocytes: Implications for host defense'. Together they form a unique fingerprint.

  • Cite this