Signal pathway regulation of interleukin-8-induced actin polymerization in neutrophils

R. L. Sham, P. D. Phatak, T. P. Ihne, C. N. Abboud, C. H. Packman

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36 Scopus citations

Abstract

Interleukin-8 (IL-8), a recently described peptide cytokine, is a neutrophil chemoattractant and activator that exerts effects similar to fMLP, yet their receptors and their roles in pathophysiology differ. The effect of IL-8 on the neutrophil cytoskeleton has not been well studied; therefore, we compared and contrasted the effects of IL-8 and fMLP on neutrophil actin conformation and on the signal pathway regulation of actin responses. IL-8 caused a rapid, dose-dependent increase in neutrophil F-actin content within 30 seconds. The maximum increase was twofold. These changes were accompanied by the development of F-actin-rich pseudopods, as noted with fluorescence microscopy and scanning electron microscopy. Selected biochemical inhibitors were used to study the regulation of the IL-8-induced actin changes. Incubation of neutrophils with 2 μg/mL pertussis toxin resulted in a 67% inhibition of the IL-8-induced F-actin increase. The protein kinase C (PKC) inhibitors, staurosporine and H7, did not inhibit the increase in F-actin caused by IL-8. IL-8 caused a rapid increase in neutrophil intracellular calcium that could be completely inhibited by the chelating agent 1,2-bis(o- aminophenoxy)ethane-N,N-N',N'-tetraacetic acid (BAPTA). However, BAPTA- treated neutrophils retained the ability to increase F-actin in response to IL-8. Similar results were seen with fMLP, indicating that, similar to fMLP, the IL-8-induced actin response is mediated through pertussis-toxin-sensitive G-proteins but is neither dependent on PKC nor increases in cytosolic calcium. Thus, although IL-8 and fMLP exert their effects on neutrophils through different receptors, the signal transduction pathways used and the effects on actin conformation and pseudopod formation are similar.

Original languageEnglish
Pages (from-to)2546-2551
Number of pages6
JournalBlood
Volume82
Issue number8
StatePublished - Jan 1 1993
Externally publishedYes

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    Sham, R. L., Phatak, P. D., Ihne, T. P., Abboud, C. N., & Packman, C. H. (1993). Signal pathway regulation of interleukin-8-induced actin polymerization in neutrophils. Blood, 82(8), 2546-2551.