Leukotriene D4 Activates Alveolar Epithelial Na,K-ATPase and Increases Alveolar Fluid Clearance

Daniel E. Sloniewsky, Karen M. Ridge, Yochai Adir, Francine P. Fries, Arturo Briva, Jacob I. Sznajder, Peter H S Sporn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Cysteinyl leukotrienes are increased during acute lung injury in animals and humans. In this study, we determined the effect of leukotriene D 4 (LTD4) on the function of Na,K-ATPase in alveolar epithelial cells and on alveolar fluid clearance in rat lungs. LTD4 (1 × 10-7 M) increased Na,K-ATPase activity at 1 and 5 minutes by 14% (p < 0.05) and 31% (p < 0.001), respectively, in A549 alveolar epithelial cells. This was accompanied by recruitment of Na,K-ATPase α1 subunits from intracellular compartment(s) to the basolateral plasma membrane. LTD4-induced α1 Na,K-ATPase membrane translocation was blocked by the dual cysteinyl LT1 (cysLT1)/ cysteinyl LT 2 (cysLT2) receptor antagonist BAY-u9773, but not by the cysLT1 antagonist MK571, implicating the cysLT2 receptor. Expression of mRNA for cysLT2, but not cysLT1, was confirmed in A549 cells and rat alveolar type 2 cells by reverse transcriptase-polymerase chain reaction. Finally, compared with control, LTD4 (1 × 10-11 M) increased alveolar fluid clearance by 41% (p < 0.001) in isolated, perfused rat lungs; this was also blocked by BAY-u9773 but not MK571. By activating alveolar epithelial Na,K-ATPase and increasing alveolar fluid reabsorption, cysteinyl leukotrienes may, in part, have a beneficial role in the acute respiratory distress syndrome.

Original languageEnglish (US)
Pages (from-to)407-412
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Issue number3
StatePublished - Feb 1 2004


  • Adult respiratory distress syndrome
  • Cysteinyl leukotriene receptors
  • Leukotriene D
  • Na(+)-K(+)-exchanging ATPase
  • Pulmonary edema

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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