Neutrophils recruit and activate human endothelial colony-forming cells at the site of vessel injury via P-selectin glycoprotein ligand-1 and L-selectin

Abstract

Background: Endothelial colony-forming cells (ECFCs) represent a subpopulation of circulating endothelial progenitor cells that have been implicated in vascular repair. However, no study has evaluated the role of ECFCs in endothelial injury leading to thrombus formation. Objective: We investigated the kinetics, mechanisms and role of ECFC recruitment in the dynamics of thrombus formation and stabilization. Methods and Results: Using digital intravital microscopy in living mice, we show that ECFCs, but not mature endothelial cells, adhere to sites of laser-induced injury and do not affect the kinetics of thrombus formation. This interaction occurs once the platelet thrombus has been stabilized, and is dependent on the presence of neutrophils but not platelets or fibrin. In vitro, the interaction of the activated neutrophils with activated endothelial cells is a prerequisite for the capture of ECFCs. Neutrophils activate ECFCs and increase their angiogenic properties, such as their ability to migrate and to form pseudocapillaries. This newly identified interaction of ECFCs with the neutrophils is mediated by the P-selectin glycoprotein ligand-1 (PSGL-1)/L-selectin axis both in vitro and in vivo. Conclusions: This study is the first demonstration that neutrophils present at the site of injury recruit ECFCs via PSGL-1/L-selectin. This interaction between neutrophils and ECFCs could play a key role in the regeneration of injured vessels in pathophysiologic conditions. © 2014 International Society on Thrombosis and Haemostasis.