LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation

Andrew T. Gewirtz, Valery V. Fokin, Nicos A. Petasis, Charles N. Serhan, James L. Madara

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The eicosanoid lipoxin A4 (LXA4) is biosynthesized in vivo by cells present at inflammatory sites and appears to be an endogenous antiinflammatory mediator. Further, in the presence of aspirin, the 15- epimer of LXA4 (15-epi-LXA4) is biosynthesized and may mediate some of aspirin's desirable bioactions. LXA4, 15-epi-LXA4, and their stable analogs inhibit inflammation in established animal models, indicating that these compounds may be useful for treating inflammatory disease states. To investigate the cellular mechanisms by which these lipid mediators downregulate inflammation, we investigated whether these eicosanoids could influence receptor-mediated degranulation of human neutrophils, an event thought to play a major causative role in several inflammatory disease states. LXA4, 15-epi-LXA4, and their stable analogs potently (IC50 <1 nM) and selectively downregulated neutrophil release of azurophilic granule contents but did not affect other neutrophil secretory functions. Thus the cellular basis of action of these natural off-switches to inflammation appears to involve downregulation of neutrophil azurophilic granule release.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number4 45-4
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Aspirin
Down-Regulation
Neutrophils
Eicosanoids
Inflammation
Inflammation Mediators
Inhibitory Concentration 50
lipoxin A4
Animals
Anti-Inflammatory Agents
Animal Models
Switches
Lipids

Keywords

  • Anti-inflammatory mediators
  • Eicosanoids
  • Elastase
  • Fcγ receptors
  • Immune complexes
  • Neutrophils

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation. / Gewirtz, Andrew T.; Fokin, Valery V.; Petasis, Nicos A.; Serhan, Charles N.; Madara, James L.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 4 45-4, 1999.

Research output: Contribution to journalArticle

Gewirtz, Andrew T. ; Fokin, Valery V. ; Petasis, Nicos A. ; Serhan, Charles N. ; Madara, James L. / LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation. In: American Journal of Physiology - Cell Physiology. 1999 ; Vol. 276, No. 4 45-4.
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