HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print November 1, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0506311v1 81/2/449    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fuhler, G. M. Articles by Vellenga, E. Search for Related Content PubMed PubMed Citation Articles by Fuhler, G. M. Articles by Vellenga, E.

(Journal of Leukocyte Biology. 2007;81:449-457.)
© 2007 by Society for Leukocyte Biology

The reduced GM-CSF priming of ROS production in granulocytes from patients with myelodysplasia is associated with an impaired lipid raft formation

Gwenny M. Fuhler^*, Nel R. Blom^*,, Paul J. Coffer, A. Lyndsay Drayer and Edo Vellenga^*,1

^* Division of Hematology, Department of Medicine, University Medical Center Groningen, Groningen, the Netherlands;
Laboratory of Cell Biology and Electron Microscopy, University of Groningen, Groningen, the Netherlands;
Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; and
Sanquin Blood Bank North East Netherlands, Groningen, the Netherlands

¹ Correspondence: Division of Hematology, Department of Medicine, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands. E-mail: e.vellenga{at}int.umcg.nl

Patients with myelodysplasia (MDS) show an impaired reactive oxygen species (ROS) production in response to fMLP stimulation of GM-CSF-primed neutrophils. In this study, we investigated the involvement of lipid rafts in this process and showed that treatment of neutrophils with the lipid raft-disrupting agent methyl-ß-cyclodextrin abrogates fMLP-induced ROS production and activation of ERK1/2 and protein kinase B/Akt, two signal transduction pathways involved in ROS production in unprimed and GM-CSF-primed neutrophils. We subsequently showed that there was a decreased presence of Lyn, gp91^phox, and p22^phox in lipid raft fractions from neutrophils of MDS. Furthermore, the plasma membrane expression of the lipid raft marker GM1, which increases upon stimulation of GM-CSF-primed cells with fMLP, was reduced significantly in MDS patients. By electron microscopy, we showed that the fMLP-induced increase in GM1 expression in GM-CSF-primed cells was a result of de novo synthesis, which was less efficient in MDS neutrophils. Taken together, these data indicate an involvement of lipid rafts in activation of signal transduction pathways leading to ROS production and show that in MDS neutrophils, an impaired lipid raft formation in GM-CSF-primed cells results in an impaired ROS production.

Key Words: MDS • signal transduction • NADPH

This article has been cited by other articles:

				G. M. Fuhler, A. L. Drayer, S. G. M. Olthof, J. J. Schuringa, P. J. Coffer, and E. Vellenga Reduced activation of protein kinase B, Rac, and F-actin polymerization contributes to an impairment of stromal cell derived factor-1 induced migration of CD34+ cells from patients with myelodysplasia Blood, January 1, 2008; 111(1): 359 - 368. [Abstract] [Full Text] [PDF]