Eotaxin is a potent chemokine that acts via CC chemokine receptor 3 (CCR3)to induce chemotaxis, mainly on eosinophils. Here we show that eotaxin also induces chemotactic migration in rat basophilic leukemia (RBL-2H3) mast cells. This effect was dose-dependently inhibited by compound X, a selective CCR3 antagonist, indicating that, as in eosinophils, the effect was mediated by CCR3. Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing adominant negative Rac1 mutant, suggesting a crucial role for Rac1 in eotaxin signaling to chemotactic migration. ERK activation also proved essential for eotaxin signaling and it too was absent in RBL-RacN17 cells. Finally, we found that activation of Rac and ERK was correlated with eotaxin-induced actin reorganization known to be necessary for cell motility. It thus appears that Rac1 acts upstream of ERK to signal chemotaxis in these cells, and that a Rac-ERK-dependent cascade mediates the eotaxin-induced chemotactic motility of RBL-2H3 mast cells.
|Number of pages||6|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - 2002|
Bibliographical noteFunding Information:
This work was supported by a Korea University Grant (2002, to J.H. Kim) and grants from the Basic Research Program (RO2-2002-000-00029-0), the Interdisciplinary Research Program (R01-1999-00097), the SRC program (Aging and Apoptosis Research Center) to Seoul National University, College of Medicine (2002) of the Korea Science and Engineering Foundation (KOSEF), and the Proteomics (Frontier 21) Project from the Ministry of Science and Technology.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology