Regulation of 5-lipoxygenase activity in mononuclear phagocytes: Characterization of an endogenous cytosolic inhibitor

Michael J. Coffey*, Steven E. Wilcoxen, Peter H. Sporn, Marc Peters-Golden

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The proinflammatory leukotrienes (LT) play important roles in host defense and disease states. However, no endogenous mechanisms to downregulate 5-lipoxygenase (5-LO), the enzyme catalyzing LT synthesis, have been described. We observed that the cytosolic fraction of rat alveolar macrophages (AMs) and peritoneal macrophages (PMs), and of peripheral blood monocytes (PBMs) contain substantial amounts of 5-LO protein, but little detectable 5-LO activity. We therefore examined these mononuclear phagocyte (MNP) cytosolic fractions for inhibitory activity against 5-LO. MNP cytosol dose-dependently reduced the 5-LO activity in neutrophil (PMN) cytosol and AM membrane. Furthermore, MNP cytosol dose-dependently prolonged the lag phase of soybean lipoxygenase (LO) without affecting the rate of product formation. This effect was overcome by subsequent addition of 13(S)-hydroperoxy-9-cis- 11-trans-octadecadienoic acid (13-HpOD), suggesting that the active factor scavenges hydroperoxides. Inactivation by boiling and proteinase K suggest that is a protein. We speculate that this cytosolic factor(s) may serve as an endogenous means for the down-regulation of 5-LO in macrophages.

Original languageEnglish (US)
Pages (from-to)103-117
Number of pages15
JournalProstaglandins and Other Lipid Mediators
Volume56
Issue number2-3
DOIs
StatePublished - Jun 1 1998

Keywords

  • Eicosanoid
  • Leukotriene
  • Lung
  • Macrophage
  • Monocyte

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulation of 5-lipoxygenase activity in mononuclear phagocytes: Characterization of an endogenous cytosolic inhibitor'. Together they form a unique fingerprint.

Cite this