Physiological Levels of Pentraxin 3 and Albumin Attenuate Vascular Endothelial Cell Damage Induced by Histone H3 In Vitro.

Abstract

Extracellular histones have strong toxicity against the vascular ECs, however, the damage is significantly attenuated in the serum. Although several plasma proteins such as albumin, APC, and PTX3 are known to inhibit the actions of histones, it is still unclear as to which plasma proteins play predominant role. The purpose of this study was to search for the major inhibitors in the serum. ECs were cultured in serum-free medium and histone H3 was added. The effects of albumin, low-, medium-, and high-concentration of APC and PTX3 were examined by time-lapse morphological observation and by immunofluorescent staining. The treatment effects were also assessed by the cell viability assay. Both 5% and 2.5% albumin, medium- and high-concentration APC, and medium- and high-concentration PTX3 exerted significant protective effect. In case of damage induced by high-concentration histone H3, all of albumin, APC and PTX3 exerted effects in a concentration-dependent manner. Above results were also confirmed by the cell viability assay. Because albumin and PTX3 inhibited histone-induced damage at physiological levels found in serum, these proteins are expected to be major histone inhibitors in vivo.