Regulation of human eosinophil NADPH oxidase activity: A central role for PKCδ

Jennifer L. Bankers-Fulbright, Hirohito Kita, Gerald J. Gleich, Scott M. O'Grady

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Eosinophils play a primary role in the pathophysiology of asthma. In the lung, the activation state of the infiltrating eosinophils determines the extent of tissue damage. Interleukin-5 (IL-5) and leukotriene B4 (LTB4) are important signaling molecules involved in eosinophil recruitment and activation. However, the physiological processes that regulate these activation events are largely unknown. In this study we have examined the mechanisms of human eosinophil NADPH oxidase regulation by IL-5, LTB4, and phorbol ester (PMA). These stimuli activate a Zn2+-sensitive plasma membrane proton channel, and treatment of eosinophils with Zn2+ blocks superoxide production. We have demonstrated that eosinophil intracellular pH is not altered by IL-5 activation of NADPH oxidase. Additionally, PKCδ inhibitors block PMA, IL-5 and LTB4 mediated superoxide formation. Interestingly, the PKCδ-selective inhibitor, rottlerin, does not block proton channel activation by PMA indicating that the oxidase and the proton conductance are regulated at distinct phosphorylation sites. IL-5 and LTB4, but not PMA, stimulated superoxide production is also blocked by inhibitors of PI 3-kinase indicating that activation of this enzyme is an upstream event common to both receptor signaling pathways. Our results indicate that the G-protein-coupled LTB4 receptor and the IL-5 cytokine receptor converge on a common signaling pathway involving PI 3-kinase and PKCδ to regulate NADPH oxidase activity in human eosinophils.

Original languageEnglish (US)
Pages (from-to)306-315
Number of pages10
JournalJournal of Cellular Physiology
Volume189
Issue number3
DOIs
StatePublished - 2001

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NADPH Oxidase
Interleukin-5
Eosinophils
Leukotriene B4
Chemical activation
Superoxides
Protons
Phosphatidylinositol 3-Kinases
Leukotriene B4 Receptors
Interleukin-5 Receptors
Phosphorylation
Cytokine Receptors
Physiological Phenomena
Phorbol Esters
Cell membranes
Enzyme Activation
GTP-Binding Proteins
Ion Channels
Human Activities
Oxidoreductases

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Regulation of human eosinophil NADPH oxidase activity : A central role for PKCδ. / Bankers-Fulbright, Jennifer L.; Kita, Hirohito; Gleich, Gerald J.; O'Grady, Scott M.

In: Journal of Cellular Physiology, Vol. 189, No. 3, 2001, p. 306-315.

Research output: Contribution to journalArticle

Bankers-Fulbright, Jennifer L. ; Kita, Hirohito ; Gleich, Gerald J. ; O'Grady, Scott M. / Regulation of human eosinophil NADPH oxidase activity : A central role for PKCδ. In: Journal of Cellular Physiology. 2001 ; Vol. 189, No. 3. pp. 306-315.
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