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Impact of engagement of FcepsilonRI and CC chemokine receptor 1 on mast cell activation and motility.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2004 Nov 12; Vol. 279 (46), pp. 48443-8. Date of Electronic Publication: 2004 Aug 26. - Publication Year :
- 2004
-
Abstract
- CC chemokines participate in the recruitment and activation of immune cells through CC chemokine receptors (CCRs). Here, we report that cross-talk between CCR1-mediated signaling pathway and FcepsilonRI-mediated signaling pathway affects degranulation positively but affects chemotaxis of mast cells adversely. Costimulation via FcepsilonRI engagement with IgE/antigen and CCR1 engagement with recombinant human CCL3 synergistically enhanced degranulation in rat basophilic leukemia-2H3 cells expressing human CCR1 (RBL-CCR1). Interestingly, FcepsilonRI engagement inhibited CCL3-mediated chemotaxis and membrane ruffling of RBL-CCR1 cells. Small GTP-binding proteins of the Rho family, Rac, Cdc42, and Rho control chemotaxis by mediating the reorganization of the actin cytoskeleton. Both a Rho inhibitor C3 exoenzyme and a Rho kinase (ROCK) inhibitor Y-27632 inhibited chemotaxis of RBL-CCR1 cells toward CCL3, indicating that activation of the Rho/ROCK signaling pathway is required for the CCL3-mediated chemotaxis of the cells. Costimulation with IgE/antigen and CCL3 enhanced Rac and Cdc42 activation but decreased ROCK activation in RBL-CCR1 cells compared with that in the cells stimulated with CCL3 alone. These results suggest that costimulation via FcepsilonRI and CCR1 engagements induced 1) inhibition of membrane ruffling, 2) decreased ROCK activation, and 3) reciprocal imbalance between Small GTP-binding proteins of the Rho family, which result in the inhibition of chemotaxis of RBL-CCR1 cells. The cross-talk between FcepsilonRI-mediated signaling pathway and CCR-mediated signaling pathway would induce optimal activation and arrested chemotaxis of mast cells, thus contributing to allergic inflammation.
- Subjects :
- Animals
Cell Degranulation physiology
Cell Line, Tumor
Chemokines, CC immunology
Enzyme Activation
Humans
Intracellular Signaling Peptides and Proteins
Mast Cells ultrastructure
Protein Serine-Threonine Kinases antagonists & inhibitors
Protein Serine-Threonine Kinases metabolism
Rats
Receptors, CCR1
Receptors, Chemokine genetics
cdc42 GTP-Binding Protein metabolism
rac GTP-Binding Proteins metabolism
rho GTP-Binding Proteins antagonists & inhibitors
rho GTP-Binding Proteins metabolism
rho-Associated Kinases
Cell Movement physiology
Mast Cells immunology
Receptors, Chemokine immunology
Receptors, IgE immunology
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 279
- Issue :
- 46
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15337751
- Full Text :
- https://doi.org/10.1074/jbc.M408725200