title: Physiological Levels of Pentraxin 3 and Albumin Attenuate Vascular Endothelial Cell Damage Induced by Histone H3 In Vitro.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
authors.affiliation: Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.affiliation: Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
authors.affiliation: Department of Surgery, Juntendo Shizuoka Hospital, Juntendo University Graduate School of Medicine, Izunokuni-shi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Liverpool, UK.
authors.forename: Jecko
authors.initials: J
authors.lastname: Thachil
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D000418:Albumins; D002097:C-Reactive Protein; D006657:Histones; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: activated protein C; albumin; endothelial cell; histone; pentraxin 3