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

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.

Antifungal activity of steroidal glycosides from Yucca gloriosa L.

The antifungal activity of a crude steroidal glycoside extract from Yucca gloriosa flowers, named alexin, was investigated in vitro against a panel of human pathogenic fungi, yeasts as well as dermatophytes and filamentous species. The minimal inhibitory concentration (MIC) was determined by an agar dilution method. Alexin had a broad spectrum of antifungal activity, found to reside entirely in the spirostanoid fraction. The major tigogenyl glycosides, yuccaloeside B and yuccaloeside C, exhibited MICs between 0.39 and 6.25 microg[sol ]mL for all the tested yeast strains except for two (C. lusitaniae and C. kefyr). They were also active against several clinical Candida isolates known to be resistant to the usual antifungal agents. The MICs for the dermatophytes were between 0.78 and 12.5 microg[sol ]mL. The most sensitive filamentous species was A. fumigatus (MIC = 1.56 microg[sol ]mL). For most of the strains, the MICs of both glycosides were similar to those of the reference antifungal agent.