Arachidonic acid in postshock mesenteric lymph induces pulmonary synthesis of leukotriene B4

Janeen R. Jordan, Ernest E. Moore, Eric L. Sarin, Sagar S. Damle, Sara B. Kashuk, Christopher C. Silliman, Anirban Banerjee

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42 Scopus citations

Abstract

Mesenteric lymph is the mechanistic link between splanchnic hypoperfusion and acute lung injury (ALI), but the culprit mediator(s) remains elusive. Previous work has shown that administration of a phospholipase A2 (PLA2) inhibitor attenuated postshock ALI and also identified a non-ionic lipid within the postshock mesenteric lymph (PSML) responsible for polymorphonuclear neutrophil (PMN) priming. Consequently, we hypothesized that gut-derived leukotriene B4 (LTB4) is a key mediator in the pathogenesis of ALI. Trauma/hemorrhagic shock (T/HS) was induced in male Sprague-Dawley rats and the mesenteric duct cannulated for lymph collection/diversion. PSML, arachidonic acid (AA), and a LTB4 receptor antagonist were added to PMNs in vitro. LC/MS/MS was employed to identify bioactive lipids in PSML and the lungs. T/HS increased AA in PSML and increased LTB4 and PMNs in the lung. Lymph diversion decreased lung LTB4 by 75% and PMNs by 40%. PSML stimulated PMN priming (11.56 ± 1.25 vs. 3.95 ± 0.29 nmol O2-/min; 3.75 × 105 cells/ml; P < 0.01) that was attenuated by LTB 4 receptor blockade (2.64 ± 0.58; P < 0.01). AA stimulated PMNs to produce LTB4, and AA-induced PMN priming was attenuated by LTB4 receptor antagonism. Collectively, these data indicate that splanchnic ischemia/reperfusion activates gut PLA2-mediated release of AA into the lymph where it is delivered to the lungs, provoking LTB 4 production and subsequent PMN-mediated lung injury.

Original languageEnglish
Pages (from-to)1161-1166
Number of pages6
JournalJournal of Applied Physiology
Volume104
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

Keywords

  • Acute lung injury
  • Hemorrhagic shock
  • Intestinal hypoperfusion
  • Multiple organ failure
  • Neutrophils

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