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Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1138-1143
Published online before print April 16, 2009, doi: 10.1161/ATVBAHA.109.187567
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1138.)
© 2009 American Heart Association, Inc.


Cell Biology/Signaling

Augmentation of Megakaryocyte Expression of Fc{gamma}RIIa by Interferon {gamma}

David J. Schneider; Heidi S. Taatjes-Sommer

From the Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington.

Correspondence to David J. Schneider, MD, University of Vermont, 208 South Park Drive, Suite 2, Colchester, VT 05446. E-mail david.schneider{at}uvm.edu

Objective— The purpose of this study was to identify factors that alter expression of Fc{gamma}RIIa by megakaryocytes.

Methods and Results— Effects of selected cytokines and growth factors on megakaryocyte expression of Fc{gamma}RIIa were assessed with phorbol 12-myristate 13-acetate (PMA)-differentiated human erythroleukemia (HEL) cells and with thrombopoietin-differentiated CD34 stem cells and compared with those obtained with myelocytic cell lines and a monocytic cell lines. Expression of Fc{gamma}RIIa was quantified with the use of Western blots and real-time reverse transcriptase-polymerase chain reaction. Megakaryocyte differentiation was identified by expression of CD41, CD42, and von Willebrand factor with the use of flow cytometry. Interferon (IFN) {gamma} increased protein expression of Fc{gamma}RIIa by HEL cells and CD34 stem cells after megakaryocyte differentiation (maximal {approx}4-fold, P<0.001 for each). IFN{gamma} did not increase expression of Fc{gamma}RIIa by undifferentiated HEL and CD34 cells. Expression of Fc{gamma}RIIa mRNA was increased (2-fold, P<0.001) in megakaryocyte-differentiated HEL cells. IFN{gamma} did not increase expression of Fc{gamma}RIIa by undifferentiated myelocytic or monocytic cell lines.

Conclusions— IFN{gamma} appears to selectively increase expression of Fc{gamma}RIIa by cells exhibiting characteristics of megakaryocytes. This effect of IFN{gamma} may contribute to greater platelet expression of Fc{gamma}RIIa in patients with atherosclerotic vascular disease.

To identify factors that alter expression of Fc{gamma}RIIa by megakaryocytes, we exposed human erythroleukemia (HEL) cells and CD34 stem cells to selected cytokines and growth factors. Interferon {gamma} increased protein and mRNA expression of Fc{gamma}RIIa by HEL cells and protein expression in CD34 stem cells exhibiting megakaryocyte characteristics.


Key Words: atherosclerosis • Fc{gamma}R • inflammation • platelets • megakaryocytes