Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor cells. Export

@article{citeulike:2875549, abstract = {Endothelial progenitor cells (EPCs) and hematopoietic progenitor cells are recruited to ischemic regions, improving neovascularization. beta1 and beta2 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 gamma (PI3Kgamma) is the PI3K isoform that selectively transduces signals from G protein-coupled receptors. Here, we investigated the role of PI3Kgamma as a signaling intermediate in the chemokine-induced integrin-dependent homing functions of progenitor cells. A pharmacological PI3Kgamma inhibitor significantly reduced chemokine-induced chemotaxis and stromal cell-derived factor (SDF)1alpha-induced transmigration of human EPCs. Moreover, the PI3Kgamma inhibitor significantly reduced SDF1alpha-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 PI3Kgamma-deficient mice that displayed reduced SDF1alpha-induced migration and intercellular adhesion molecule-1 adhesion as compared with wild-type cells. Pharmacological inhibition or genetic ablation of PI3Kgamma reduced SDF1alpha-induced integrin activation in human EPCs and in murine Lin(-) BM-derived progenitor cells, respectively. In vivo, the homing of PI3Kgamma-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, PI3Kgamma is integral to the integrin-dependent homing of progenitor cells.}, address = {Molecular Cardiology, Department of Internal Medicine III, J. W. Goethe University of Frankfurt, Theodor Stern-Kai 7, 60590 Frankfurt, Germany. Chavakis@em.uni-frankfurt.de}, author = {Chavakis, E. and Carmona, G. and Urbich, C. and G\"{o}ttig, S. and Henschler, R. and Penninger, J. M. and Zeiher, A. M. and Chavakis, T. and Dimmeler, S.}, citeulike-article-id = {2875549}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/CIRCRESAHA.107.164376}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18323525}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18323525}, day = {25}, doi = {10.1161/CIRCRESAHA.107.164376}, issn = {1524-4571}, journal = {Circulation research}, keywords = {p110g}, month = {April}, number = {8}, pages = {942--949}, posted-at = {2008-06-09 13:20:06}, priority = {2}, title = {Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor cells.}, url = {http://dx.doi.org/10.1161/CIRCRESAHA.107.164376}, volume = {102}, year = {2008} }

TY - JOUR ID - citeulike:2875549 L3 - citeulike-article-id:2875549 N2 - Endothelial progenitor cells (EPCs) and hematopoietic progenitor cells are recruited to ischemic regions, improving neovascularization. beta1 and beta2 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 gamma (PI3Kgamma) is the PI3K isoform that selectively transduces signals from G protein-coupled receptors. Here, we investigated the role of PI3Kgamma as a signaling intermediate in the chemokine-induced integrin-dependent homing functions of progenitor cells. A pharmacological PI3Kgamma inhibitor significantly reduced chemokine-induced chemotaxis and stromal cell-derived factor (SDF)1alpha-induced transmigration of human EPCs. Moreover, the PI3Kgamma inhibitor significantly reduced SDF1alpha-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 PI3Kgamma-deficient mice that displayed reduced SDF1alpha-induced migration and intercellular adhesion molecule-1 adhesion as compared with wild-type cells. Pharmacological inhibition or genetic ablation of PI3Kgamma reduced SDF1alpha-induced integrin activation in human EPCs and in murine Lin(-) BM-derived progenitor cells, respectively. In vivo, the homing of PI3Kgamma-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, PI3Kgamma is integral to the integrin-dependent homing of progenitor cells. IS - 8 JF - Circulation research SN - 1524-4571 AD - Molecular Cardiology, Department of Internal Medicine III, J. W. Goethe University of Frankfurt, Theodor Stern-Kai 7, 60590 Frankfurt, Germany. Chavakis@em.uni-frankfurt.de EP - 949 TI - Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor cells. VL - 102 SP - 942 KW - p110g AU - Chavakis, E AU - Carmona, G AU - Urbich, C AU - Göttig, S AU - Henschler, R AU - Penninger, JM AU - Zeiher, AM AU - Chavakis, T AU - Dimmeler, S PY - 2008/04/25/ UR - http://dx.doi.org/10.1161/CIRCRESAHA.107.164376 ER -