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  • Title: Leukotriene D4 activates alveolar epithelial Na,K-ATPase and increases alveolar fluid clearance.
    Author: Sloniewsky DE, Ridge KM, Adir Y, Fries FP, Briva A, Sznajder JI, Sporn PH.
    Journal: Am J Respir Crit Care Med; 2004 Feb 01; 169(3):407-12. PubMed ID: 14578215.
    Abstract:
    Cysteinyl leukotrienes are increased during acute lung injury in animals and humans. In this study, we determined the effect of leukotriene D4 (LTD4) on the function of Na,K-ATPase in alveolar epithelial cells and on alveolar fluid clearance in rat lungs. LTD4 (1 x 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 alpha1 subunits from intracellular compartment(s) to the basolateral plasma membrane. LTD4-induced alpha1 Na,K-ATPase membrane translocation was blocked by the dual cysteinyl LT1 (cysLT1)/ cysteinyl LT3 (cysLT3) receptor antagonist BAY-u9773, but not by the cysLT1 antagonist MK571, implicating the cysLT3 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 x 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.
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