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Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor cells
- Source :
- Circulation research. 102(8)
- Publication Year :
- 2008
-
Abstract
- Endothelial progenitor cells (EPCs) and hematopoietic progenitor cells are recruited to ischemic regions, improving neovascularization. β1 and β2 integrins play a crucial role for progenitor cell homing to ischemic tissues. Integrin activity is regulated by chemokines and their respective G protein–coupled receptors. The phosphatidylinositol-3-kinase catalytic subunit γ (PI3Kγ) is the PI3K isoform that selectively transduces signals from G protein–coupled receptors. Here, we investigated the role of PI3Kγ as a signaling intermediate in the chemokine-induced integrin-dependent homing functions of progenitor cells. A pharmacological PI3Kγ inhibitor significantly reduced chemokine-induced chemotaxis and stromal cell–derived factor (SDF)1α-induced transmigration of human EPCs. Moreover, the PI3Kγ inhibitor significantly reduced SDF1α-induced adhesion of EPCs to intercellular adhesion molecule-1 and human umbilical vein endothelial cell monolayers. These findings were corroborated with Lin−bone marrow–derived progenitor cells from PI3Kγ-deficient mice that displayed reduced SDF1α-induced migration and intercellular adhesion molecule-1 adhesion as compared with wild-type cells. Pharmacological inhibition or genetic ablation of PI3Kγ reduced SDF1α-induced integrin activation in human EPCs and in murine Lin−BM-derived progenitor cells, respectively. In vivo, the homing of PI3Kγ-deficient Lin−progenitor cells to ischemic muscles after intravenous infusion in the model of hindlimb ischemia and their neovascularization-promoting capacity was reduced as compared with wild-type cells. In conclusion, PI3Kγ is integral to the integrin-dependent homing of progenitor cells.
- Subjects :
- Chemokine
Integrins
Umbilical Veins
Stromal cell
Physiology
Integrin
Biology
Mice
Phosphatidylinositol 3-Kinases
Ischemia
Cell Adhesion
Animals
Class Ib Phosphatidylinositol 3-Kinase
Humans
Progenitor cell
Muscle, Skeletal
Cells, Cultured
Mice, Knockout
Chemotaxis
Stem Cells
Chemokine CXCL12
Cell biology
Endothelial stem cell
Isoenzymes
Biochemistry
biology.protein
Human umbilical vein endothelial cell
Cattle
Cardiology and Cardiovascular Medicine
Cell Adhesion Molecules
Homing (hematopoietic)
Signal Transduction
Subjects
Details
- ISSN :
- 15244571
- Volume :
- 102
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Circulation research
- Accession number :
- edsair.doi.dedup.....fd4eb39648ee580d0448a9e3091f585d