Volume 67, Issue 3 p. 396-404
Journal Article
Free Access

Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase

Anna Karlsson

Corresponding Author

Anna Karlsson

The Phagocyte Research Laboratory, Department of Medical Microbiology and Immunology, University of Göteborg, Sweden

Correspondence: Anna Karlsson, Ph.D., The Phagocyte Research Laboratory, Dept. of Medical Microbiology and Immunology, Guldhedsgatan 10, S-413 46 Göteborg, Sweden. E-mail: [email protected]Search for more papers by this author
Jennifer B. Nixon

Jennifer B. Nixon

Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina

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Linda C. McPhail

Linda C. McPhail

Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina

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First published: 01 March 2000
Citations: 157

Abstract

The neutrophil NADPH-oxidase can be activated by protein kinase C (PKC) agonists such as phorbol myristate acetate (PMA), resulting in superoxide anion release. This superoxide release is independent of phosphatidylinositol 3-kinase (PI 3-kinase) because the inhibitor wortmannin does not affect the response. In this study, PMA is shown to also induce a wortmannin-sensitive NADPH-oxidase activation, however, not resulting in release of superoxide but in intracellular production of the radical. This indicates that two pools of NADPH-oxidase, one localized in the plasma membrane and the other in the granule membranes, are separately regulated and the signal transduction pathways leading to activation of these pools differ regarding involvement of PI 3-kinase. Activation of both pools was dependent on ERK/MAPK kinase (MEK) activity and protein phosphatase 1 and/or 2A. As the two oxidase responses were differently affected by the inhibitor Gö-6850, different PKC isozymes are suggested to take part in the two signal transduction pathways. J. Leukoc. Biol. 67: 396–404; 2000.