The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pike, M. C.
Right arrow Articles by Lamb, K. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pike, M. C.
Right arrow Articles by Lamb, K. A.

The Journal of Immunology, Vol 148, Issue 10 3158-3164, Copyright © 1992 by American Association of Immunologists

ARTICLES

IL-8 stimulates phosphatidylinositol-4-phosphate kinase in human polymorphonuclear leukocytes

MC Pike, KM Costello and KA Lamb
Arthritis Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.

IL-8 is a neutrophil-specific chemoattractant and cellular activator which exists in at least three forms, 69, 72, and 77 amino acids. The predominant monocyte product has 72 amino acids, whereas endothelial cells secrete the 77-amino acid form. The 72-amino acid form has been shown to increase intracellular calcium in neutrophils, but the exact biochemical pathways involved in stimulation of these cells is unknown. N-formyl peptide chemoattractants in neutrophils stimulate the formation of phosphatidylinositol-4,5-bisphosphate (PIP2), a reservoir for second messenger molecules and regulator of actin assembly through its association with the actin-binding proteins, profilin, and gelsolin. The present study examined whether IL-8 altered the enzyme which synthesizes PIP2, phosphatidylinositol-4-phosphate (PIP) kinase. Incubation of intact neutrophils with 10 nM IL-8 caused approximately a twofold increase in the activity of the enzyme. All forms of IL-8 stimulated PIP kinase activity in concentrations ranging from 1 to 50 nM, and the dose-response curves exactly correlated with the order of potency of these cytokines for interacting with the IL-8R on the surface of neutrophils. Lineweaver-Burk analysis of the kinetics of PIP kinase assayed in the presence of 0.03 to 0.7 mM ATP showed that 10 nM IL-8 increased the Vmax of the enzyme 38 to 70.5%, with no significant change in the apparent Km for ATP or for PIP. The stimulation of PIP kinase activity could not be explained by decreased degradation of PIP2 by phospholipase C or phosphomonoesterase activity in the membranes isolated from cells treated with IL-8 or by a decrease in the degradation of ATP. The microfilament disrupter, cytochalasin b, inhibited IL-8 induced stimulation of PIP kinase. These findings demonstrate that all forms of IL-8 stimulate PIP kinase in human neutrophils. This event may provide molecular signals to these cells that are necessary to maintain or change the state of microfilament assembly during cellular activation.


This article has been cited by other articles:


Home page
 BloodHome page
R. Feniger-Barish, D. Belkin, A. Zaslaver, S. Gal, M. Dori, M. Ran, and A. Ben-Baruch
GCP-2-induced internalization of IL-8 receptors: hierarchical relationships between GCP-2 and other ELR+-CXC chemokines and mechanisms regulating CXCR2 internalization and recycling
Blood, March 1, 2000; 95(5): 1551 - 1559.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Ben-Baruch, D. F. Michiel, and J. J. Oppenheim
Signals and Receptors Involved in Recruitment of Inflammatory Cells
J. Biol. Chem., May 19, 1995; 270(20): 11703 - 11706.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1992 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1992 by The American Association of Immunologists, Inc. All rights reserved.