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

Результат исследований: Материалы для журналаСтатья

56 Цитирования (Scopus)

Аннотация

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.

Язык оригиналаАнглийский
ЖурналAmerican Journal of Physiology - Cell Physiology
Том276
Номер выпуска4 45-4
СостояниеОпубликовано - 1999
Опубликовано для внешнего пользованияДа

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ASJC Scopus subject areas

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

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