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Related Experiment Videos

Polyisoprenyl phosphates in intracellular signalling

B D Levy1, N A Petasis, C N Serhan

  • 1Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Nature
|November 14, 1997
PubMed
Summary

Researchers discovered presqualene diphosphate (PSDP) as a novel intracellular lipid signal regulating oxygen-radical formation in neutrophils. This finding reveals PSDP

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Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Leukocyte membrane remodeling produces lipids mediating inflammatory responses.
  • Neutrophils play a key role in host defense, inflammation, and tissue injury through oxygen-radical formation.

Purpose of the Study:

  • To identify novel intracellular lipid signals regulating neutrophil function.
  • To characterize the role of phosphorylated lipids in neutrophil superoxide anion production.

Main Methods:

  • Screening of neutrophil-derived lipids for inhibitors of superoxide anion production.
  • Structural analysis of active lipid fractions.
  • Total organic synthesis of identified lipids (presqualene diphosphate and presqualene monophosphate).
  • Testing the inhibitory effects of synthesized lipids on cell-free neutrophil oxidase preparations.

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Main Results:

  • A potent inhibitor of superoxide anion production was identified in neutrophil extracts.
  • Presqualene diphosphate (PSDP) was the most abundant phosphorylated lipid identified.
  • PSDP, but not its monophosphate form (PSMP), inhibited superoxide anion production at submicromolar concentrations.
  • Synthesized PSDP and PSMP matched the properties and activity of neutrophil-derived compounds.

Conclusions:

  • Presqualene diphosphate (PSDP), a cholesterol biosynthesis intermediate, is present in immune effector cells.
  • PSDP acts as a potent regulator of neutrophil oxygen-radical production, impacting host defense mechanisms.