2006年
The role of platelet-derived growth factor receptor in eotaxin signaling of eosinophils
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
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- 巻
- 140
- 号
- 開始ページ
- 28
- 終了ページ
- 34
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1159/000092708
- 出版者・発行元
- KARGER
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 PDGFRP mRNA in 4 out of 8 donors, while PDGFR alpha 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 PDGFRP 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. Copyright (c) 2006 S. Karger AG, Basel.
- リンク情報
- ID情報
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- DOI : 10.1159/000092708
- ISSN : 1018-2438
- PubMed ID : 16772724
- Web of Science ID : WOS:000238477900006