Submitted June 20, 2006
Accepted November 19, 2006
c-Kit by interacting with the membrane-bound ligand recruits endothelial progenitor cells to inflamed endothelium
Patrizia Dentelli, Arturo Rosso, Antonina Balsamo, Sofia Colmenares Benedetto, Annarita Zeoli, Marco Pegoraro, Giovanni Camussi, Luigi Pegoraro, and Maria Felice Brizzi*
Dept of Internal Medicine, University of Torino, Torino, Italy
Division of Vascular Surgery, Ospedale Molinette, Torino, Italy
* Corresponding author; email: mariafelice.brizzi{at}unito.it.
We investigated the role of c-Kit and of the membrane-bound ligand (mbKitL) in endothelial progenitor cell (EPC) recruitment by microvascular endothelial cells (EC). We demonstrated that inflammatory activation induced the expression of the mbKitL on EC both in vitro and in vivo, and that recruitment of EPC depended on c-Kit/mbKitL interaction. Depletion of endogenous c-Kit or inhibition of c-Kit enzymatic activity by Imatinib prevented adhesion of EPC to activated EC both in vitro and in vivo, indicating that a functional c-Kit on EPC is essential. We also demonstrate that Akt was the downstream molecule regulating cell adhesion. A potential role of the c-Kit/mbKitL interaction in pathological settings is sustained by the expression of the mbKitL on EC lining intraplaque neovessels. Thus, our results provide new insights into the mechanisms underlying EPC recruitment and the bases for novel strategies to hinder pathological angiogenesis.
