Lipoxin A4 Attenuates Microvascular Fluid Leak During Inflammation

Alexander Q. Ereso, Elizabeth L. Cureton, Michael W Cripps, Javid Sadjadi, Monica M. Dua, Brian Curran, Gregory P. Victorino

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: The release of proinflammatory cytokines during inflammation disturbs the endothelial barrier and can initiate significant intravascular volume loss. Proinflammatory cytokines also induce the expression of anti-inflammatory mediators, such as lipoxin, which promote the resolution of inflammation. Our hypothesis is that lipoxin A4 (LXA4) reverses the increased microvascular fluid leak observed during inflammatory conditions. Materials and Methods: Microvascular fluid leak (Lp) was measured in rat mesenteric venules using a micro-cannulation technique. Lp was measured under the following conditions: (1) LXA4 (100 nM) alone (n = 5), (2) LXA4 (100 nM) administered after endothelial hyperpermeability induced by a continuous perfusion of 10 nM platelet activating factor (PAF) (n = 5), (3) LXA4 (100 nM) perfused after inflammation induced by a systemic bolus of 10 mg/kg lipopolysaccharide (LPS) (n = 5), and (4) LXA4 (100 nM) perfused after LPS-induced inflammation during inhibition of c-Jun N-terminal kinase (n = 4). Results: LXA4 alone slightly increased Lp from baseline (Lp-baseline = 1.05 ± 0.03, Lp-LXA4 = 1.55 ± 0.04; P < 0.0001). PAF increased Lp 4-fold (Lp-baseline = 1.20 ± 0.10, Lp-PAF = 4.49 ± 0.95; P < 0.0001). LXA4 administration after PAF decreased Lp 66% versus PAF alone (from 4.49 ± 0.95 to 1.54 ± 0.13; P = 0.0004). LPS-induced inflammation increased Lp over 2-fold (Lp-baseline = 1.05 ± 0.03, Lp-LPS = 2.27 ± 0.13; P < 0.0001). LXA4 administration after LPS decreased Lp 42% versus LPS alone (from 2.27 ± 0.13 to 1.31 ± 0.05; P < 0.0001). The effect of c-Jun N-terminal kinase inhibition during LPS-induced inflammation attenuated the decrease in leak cause by LXA4 by 51% (P = 0.0002). Conclusion: After either LPS or PAF, LXA4 attenuated the intravascular volume loss caused by these inflammatory mediators. The activity of LXA4 may be partly mediated by the c-Jun N-terminal kinase signaling pathway. These data support an anti-inflammatory role for LXA4 and suggests a potential pharmacologic role for LXA4 during inflammation.

Original languageEnglish (US)
Pages (from-to)183-188
Number of pages6
JournalJournal of Surgical Research
Issue number2
StatePublished - Oct 2009


  • inflammation
  • lipoxins
  • lipoxin A4
  • sepsis
  • shock

ASJC Scopus subject areas

  • Surgery


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