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(Journal of Leukocyte Biology. 2003;73:191-200.)
© 2003 by Society for Leukocyte Biology

Cell type-dependent activation of 5-lipoxygenase by arachidonic acid

Eva Bürkert*, Dagmar Szellas*, Olof Rådmark{dagger}, Dieter Steinhilber* and Oliver Werz*

* Institute of Pharmaceutical Chemistry, University of Frankfurt, Germany; and
{dagger} Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institute, Stockholm, Sweden

Correspondence: Dr. Oliver Werz, Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt, Germany. E-mail: o.werz{at}pharmchem.uni-frankfurt.de

5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory leukotrienes. We show that stimulation of polymorphonuclear leukocytes (PMNL), rat basophilic leukemia (RBL)-1, or transfected HeLa cells with arachidonic acid (AA) caused prominent 5-LO product formation that coincided with the activity of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase. 5-LO product formation in AA-stimulated PMNL and RBL-1 cells was independent of Ca2+. However, in HeLa cells expressing a 5-LO mutant lacking potential 5-LO phosphorylation sites, removal of Ca2+ caused a prominent loss of 5-LO activity. For Mono Mac 6 (MM6) cells, AA failed to activate ERKs, and AA-induced 5-LO product formation was only minute. Also, activation of ERKs by phorbol esters did not lead to prominent 5-LO product synthesis. Instead, 5-LO activation in MM6 cells required Ca2+ or alternative signaling pathways induced by hyperosmotic stress. In summary, mechanisms for activation of 5-LO differ considerably between cell types.

Key Words: leukotriene • Ca2+ • MAP kinase




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