Eotaxin induces migration of RBL-2H3 mast cells via a Rac-ERK-dependent pathway.
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 a dominant 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.
Woo
Chang-Hoon
CH
Graduate School of Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul 136-701, South Korea.
Jeong
Dong Tak
DT
Yoon
Seog-Beom
SB
Kim
Key-Sun
KS
Chung
Il Yup
IY
Saeki
Toshihiko
T
Kim
Jae-Hong
JH
D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D017931:DNA Primers; D008407:Mast Cells / Q000166:cytology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D019742:Chemokines, CC; D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins