Modeling the effect of platelet concentrate supernatants on endothelial cells: focus on endocan/ESM-1.

Abstract

Platelets (PLTs) are prone to activation and the release of biologic response modifiers (BRMs) under storage conditions. The transfusion inflammatory reaction in the vascular compartment involves endothelial cell activation due to cell-cell interactions and BRMs infused with the blood products. Endocan/ESM-1 is a proteoglycan secreted by endothelial cells under the control of proinflammatory cytokines. We aimed to measure endocan activity in supernatants of PLT components (PCs), implicated in serious adverse reactions (SARs) or not (no.AR), sampled at different stages during storage. PLT function, by quantification of soluble CD62P, and their ability to produce endocan were assessed. Functional testing of PC supernatants was performed on EA.hy926 endothelial cells in vitro by exposing them to PC supernatants from each group (no.AR or SARs); EA.hy926 activation was evaluated by their production of interleukin (IL)-6 and endocan. PLT endocan secretion was not induced in response to PLT surface molecule agonists, and no significant correlation was observed between sCD62P and endocan concentration after PLT activation. However, we observed a significant increase in the secretion of IL-6 and endocan after EA.hy926 activation by all PC supernatants. IL-6 and endocan secretion were significantly higher for cells stimulated with SAR than those stimulated with no.AR PC supernatants, as well as cell apoptosis. The correlation between the secretion of endocan and that of IL-6 by endothelial cells suggests that endocan can be used as a predictive marker of inflammation for the quality assessment of transfusion grade PLTs.