Published online before print March 6, 2008, doi: 10.1161/CIRCRESAHA.107.164376
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 17, 2007
Revised on February 7, 2008
Accepted on February 27, 2008
Phosphatidylinositol-3-Kinase-
Is Integral to Homing Functions of Progenitor Cells
Emmanouil Chavakis *;
From Molecular Cardiology, Department of Internal Medicine III (E.C., G.C., C.U., A.M.Z., S.D.), and the DRK Institute of Transfusion Medicine and Immune Hematology (S.G., R.H.), J. W. Goethe University Frankfurt, Germany; the Institute for Molecular Biotechnology (J.M.P.), Vienna, Austria; and the Experimental Immunology Branch (T.C.), National Cancer Institute, NIH, Bethesda, Md.
* To whom correspondence should be addressed. E-mail: Chavakis{at}em.uni-frankfurt.de.
Endothelial progenitor cells (EPCs) and hematopoietic progenitor cells are recruited to ischemic regions, improving neovascularization. 
1 and 2 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 
(PI3K) is the PI3K isoform that selectively transduces signals from G protein–coupled receptors. Here, we investigated the role of PI3K as a signaling intermediate in the chemokine-induced integrin-dependent homing functions of progenitor cells. A pharmacological PI3K inhibitor significantly reduced chemokine-induced chemotaxis and stromal cell–derived factor (SDF)1
-induced transmigration of human EPCs. Moreover, the PI3K inhibitor significantly reduced SDF1-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 PI3K-deficient mice that displayed reduced SDF1-induced migration and intercellular adhesion molecule-1 adhesion as compared with wild-type cells. Pharmacological inhibition or genetic ablation of PI3K reduced SDF1-induced integrin activation in human EPCs and in murine Lin- BM-derived progenitor cells, respectively. In vivo, the homing of PI3K-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, PI3K is integral to the integrin-dependent homing of progenitor cells.
Key words: progenitor cells • homing • integrins • adhesion • migration • PI3K
, neovascularization
Related Article:
-
PI3K Helps an SDF Seeking Home ... for EPCs
- Ziad Mallat
Circ. Res. 2008 102: 871-872.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  F. Morello, A. Perino, and E. Hirsch Phosphoinositide 3-kinase signalling in the vascular system Cardiovasc Res, May 1, 2009; 82(2): 261 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Y. Oudit and J. M. Penninger Cardiac regulation by phosphoinositide 3-kinases and PTEN Cardiovasc Res, May 1, 2009; 82(2): 250 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Scharner, L. Rossig, G. Carmona, E. Chavakis, C. Urbich, A. Fischer, T.-B. Kang, D. Wallach, Y. J. Chiang, Y. L. Deribe, et al. Caspase-8 Is Involved in Neovascularization-Promoting Progenitor Cell Functions Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 571 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Krankel, R. G. Katare, M. Siragusa, L. S. Barcelos, P. Campagnolo, G. Mangialardi, O. Fortunato, G. Spinetti, N. Tran, K. Zacharowski, et al. Role of Kinin B2 Receptor Signaling in the Recruitment of Circulating Progenitor Cells With Neovascularization Potential Circ. Res., November 21, 2008; 103(11): 1335 - 1343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Urao, H. Inomata, M. Razvi, H. W. Kim, K. Wary, R. McKinney, T. Fukai, and M. Ushio-Fukai Role of Nox2-Based NADPH Oxidase in Bone Marrow and Progenitor Cell Function Involved in Neovascularization Induced by Hindlimb Ischemia Circ. Res., July 18, 2008; 103(2): 212 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Mallat PI3K{gamma} Helps an SDF Seeking Home ... for EPCs Circ. Res., April 25, 2008; 102(8): 871 - 872. [Full Text] [PDF]
|
|