C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium

• Published in: Blood Vol. 109; no. 10; pp. 4264 - 4271
• Main Authors: Dentelli, Patrizia, Rosso, Arturo, Balsamo, Antonina, Colmenares Benedetto, Sofia, Zeoli, Annarita, Pegoraro, Marco, Camussi, Giovanni, Pegoraro, Luigi, Brizzi, Maria Felice
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.05.2007
• Subjects: Animals; Cell Adhesion; Cells, Cultured; Coronary Artery Disease - metabolism; Endothelial Cells - metabolism; Endothelium, Vascular - metabolism; Humans; Inflammation - metabolism; Membrane Proteins - metabolism; Mice; Mice, SCID; Neovascularization, Pathologic - metabolism; Oncogene Protein v-akt - physiology; Proto-Oncogene Proteins c-kit - metabolism; Proto-Oncogene Proteins c-kit - physiology; Signal Transduction; Stem Cell Factor - metabolism; Stem Cells - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-06-029603

We investigated the role of c-Kit and the membrane-bound ligand (mbKitL) in endothelial progenitor cell (EPC) recruitment by microvascular endothelial cells (ECs). We demonstrated that inflammatory activation induced the expression of the mbKitL on ECs both in vitro and in vivo, and that recruitment of EPCs depended on c-Kit/mbKitL interaction. Depletion of endogenous c-Kit or inhibition of c-Kit enzymatic activity by imatinib mesylate prevented adhesion of EPCs to activated ECs both in vitro and in vivo, indicating that a functional c-Kit on EPCs 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 ECs 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.