Hypertonicity suppresses ionophore-induced product formation and translocation of 5-lipoxygenase in human leukocytes

J Leukoc Biol. 2002 Mar;71(3):477-86.


5-Lipoxygenase (5-LO) initiates the biosynthesis of proinflammatory leukotrienes from arachidonic acid (AA). Here, we demonstrate that hypertonicity suppresses ionophore-induced 5-LO product formation reversibly in isolated human polymorphonuclear leukocytes (PMNL) and in Mono Mac 6 cells. Hypertonicity blocked the liberation of AA and abrogated translocation of 5-LO to the nuclear membrane. Accordingly, in the presence of exogenous AA, 5-LO product formation was less affected. The effects of hypertonicity were a result of cell shrinkage and not cytosolic hyperosmolarity. Hypertonicity did not inhibit the rapid increase in intracellular Ca(2)(+) induced by ionophores but prevented the ionophore-induced activation of p38 MAPK-regulated MAPKAP kinases, which can phosphorylate and activate 5-LO (and cPLA(2)). In summary, we show that hypertonicity blocks agonist-induced release of AA, 5-LO product formation, and translocation and in parallel, prevents activation of p38 MAPK and downstream 5-LO kinases in leukocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / metabolism*
  • Arachidonic Acid / biosynthesis*
  • Cell Line
  • Glucose Solution, Hypertonic
  • Humans
  • Ionophores / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Neutrophils / metabolism*
  • Protein Transport / drug effects


  • Glucose Solution, Hypertonic
  • Ionophores
  • Arachidonic Acid
  • Arachidonate 5-Lipoxygenase