International Journal of Hematology

DOI: 10.1007/s12185-018-2402-x Pages: 1-7

Protective effect of a newly developed fucose-deficient recombinant antithrombin against histone-induced endothelial damage

1. Juntendo University Graduate School of Medicine, Department of Emergency and Disaster Medicine

2. Juntendo University Graduate School of Medicine, Department of Emergency and Disaster Medicine

3. Juntendo University Graduate School of Medicine, Department of Surgery, Juntendo Shizuoka Hospital

4. Juntendo University Graduate School of Medicine, Department of Host Defense and Biochemical Research

Correspondence to:
Toshiaki Iba
Tel: 81-3-3813-3111
Email: toshiiba@cf6.so-net.ne.jp

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Abstract

Antithrombin is expected to modulate both prothrombotic and proinflammatory reactions in sepsis; vascular endothelium is the primary target. In the present study, we sought to evaluate the protective effects of a newly developed fucose-deficient recombinant antithrombin. Endothelial cells were treated in vitro with histone H4 to induce cellular damage. Low to high doses of either plasma-derived antithrombin or recombinant thrombomodulin were used as treatment interventions. Morphological change, apoptotic rate, cell viability, cell injury, and syndecan-4 level in the medium were evaluated. Immunofluorescent staining with anti-syndecan-4 was also performed. Both types of antithrombin reduced cellular damage and apoptotic cell death. Both plasma-derived and recombinant antithrombin improved cell viability and reduced cellular injury when administered at a physiological concentration or higher. Syndecan-4 staining became evident after treatment with histone H4, and both antithrombins suppressed the staining intensity at similar levels. The syndecan-4 level in the medium was significantly decreased by both antithrombins. None of the indicators showed a significant difference between plasma-derived and recombinant antithrombin. In conclusion, both recombinant and plasma-derived antithrombin can protect vascular endothelial cells. Recombinant antithrombin may represent a useful new therapeutic agent for sepsis-associated vascular damage.

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