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Interleukin 8-Stimulated Phosphatidylinositol-3-Kinase Activity Regulates the Migration of Human Neutrophils Independent of Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinases
Cindy Knall, G. Scott Worthen and Gary L. Johnson
Proceedings of the National Academy of Sciences of the United States of America
Vol. 94, No. 7 (Apr. 1, 1997), pp. 3052-3057
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/41774
Page Count: 6
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Chemoattractants and chemokines, such as interleukin 8 (IL-8), are defined by their ability to induce directed cell migration of responsive cells. The signal transduction pathway(s) leading to cell migration remain ill defined. We demonstrate that phosphatidylinositol-3-kinase (PI3K) activity, as determined by inhibition using wortmannin and LY294002, is required for IL-8-induced cell migration of human neutrophils. Recently we reported that IL-8 caused the activation of the Ras/Raf/extracellular signal-regulated kinase (ERK) pathway in human neutrophils and that this activation was dependent on PI3K activity. The regulation of cell migration by IL-8 is independent of ERK kinase and ERK activation since the ERK kinase inhibitor PD098059 had no effect on IL-8-induced cell migration of human neutrophils. Additionally, activation of p38-mitogen-activated protein kinase is insufficient and activation of c-Jun N-terminal kinase is unnecessary to induce cell migration of human neutrophils. Therefore, regulation of neutrophil migration appears to be largely independent of the activation of the mitogen-activated protein kinases. The data argue that PI3K activity plays a central role in multiple signal transduction pathways within the human neutrophil leading to distinct cell functions.
Proceedings of the National Academy of Sciences of the United States of America © 1997 National Academy of Sciences