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Vol. 140, Suppl. 1, 2006
Issue release date: June 2006
Section title: Original Paper
Int Arch Allergy Immunol 2006;140:28–34
(DOI:10.1159/000092708)

The Role of Platelet-Derived Growth Factor Receptor in Eotaxin Signaling of Eosinophils

Adachi T. · Hanaka S. · Yano T. · Yamamura K. · Yoshihara H. · Nagase H. · Chihara J. · Ohta K.
aDepartment of Internal Medicine, Teikyo University School of Medicine, Tokyo, and bDepartment of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: 6/12/2006

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

Abstract

Background: Receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) are capable of eliciting kinase activity after ligand binding. In several cells, RTKs are activated via the G-protein-coupled receptor independent of the ligand-RTK interaction. We have previously found that EGFR is transactivated via CC chemokine receptor 3 in bronchial epithelial cells and that this pathway is important for mitogen-activated protein (MAP) kinase activation and cytokine production. It has recently been suggested that hypereosinophilic syndrome results from the fusion tyrosine kinase FIP1L1-PDGFRA. Although it is possible that the PDGFR signal is involved in eosinophil function, the details are still unclear. Methods: Blood eosinophils were purified using Percoll and anti-CD16 antibody-coated magnetic beads. Expression of PDGFR mRNA was examined by RT-PCR. After stimulating eosinophils with eotaxin, the phosphorylation of MAP kinases was examined by Western blotting with the antiphosphospecific MAP kinase antibody. The eotaxin-induced eosinophil chemotaxis was studied using Boyden chambers. Results: Eosinophils expressed PDGFRβ  mRNA in 4 out of 8 donors, while PDGFRα mRNA was expressed in only 1 donor. Protein expression of PDGFR was also detectable in eosinophils from some donors. AG1295, a specific inhibitor of PDGFR, showed dose-dependent inhibition of eotaxin-induced MAP kinase phosphorylation in the eosinophils expressing PDGFRβ mRNA. The chemotaxis of these eosinophils was significantly inhibited by AG1295 (n = 3). Conclusions: Our results suggest that PDGFR modifies the CCR3-MAP kinase signaling pathway and chemotactic response in some donors. The pharmacological targeting of PDGFR may be a new strategy to treat eosinophilic disorders.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: 6/12/2006

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


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