Inorganic polyphosphate modulates leukocyte accumulation and vascular endothelial cell permeability and ameliorates cecal ligation and puncture-induced lethality

• Yamazaki Yoshitaka

  Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy Pharmacology Research Center, Showa University

• Terashima-Hasegawa Mikako

  Division of Aesthetic Dentistry and Clinical Cariology, Department of Conservative Dentistry, Showa University School of Dentistry

• Manabe Atsufumi

  Division of Aesthetic Dentistry and Clinical Cariology, Department of Conservative Dentistry, Showa University School of Dentistry

• Shiba Toshikazu

  Division of Aesthetic Dentistry and Clinical Cariology, Department of Conservative Dentistry, Showa University School of Dentistry Regenetiss Inc.

• Kawazoe Yumi

  Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy Regenetiss Inc.

• Ashino Takashi

  Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy Pharmacology Research Center, Showa University

• Hosonuma Masahiro

  Department of Clinical Immuno-oncology, Clinical Research Institute of Clinical Pharmacology and Therapeutics, Showa University

• Numazawa Satoshi

  Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy Pharmacology Research Center, Showa University

抄録

Inorganic polyphosphates with an average degree of polymerization of 150 (polyP₁₅₀) have been shown to improve mortality in a lipopolysaccharide model of sepsis in mice. We aimed to investigate the effects of polyP₁₅₀ in a mouse model of cecal ligation and puncture (CLP) peritonitis, which accurately reflects clinical sepsis, and elucidate its mechanism of action and suitability as a candidate for sepsis treatment. The present study demonstrated that treatment with polyP₁₅₀ significantly improved survival rate in mouse model of CLP peritonitis. polyP₁₅₀ inhibited a CLP-mediated increase in pulmonary vascular permeability as demonstrated by Evans blue dye assay. Pretreatment of polyP₁₅₀ in human vascular endothelial cells, HMEC-1 cells, showed inhibition of tumor necrosis factor-α-induced monocytic THP-1 cell adhesion and intercellular adhesion molecule 1/CD54 gene expression. These results suggest that polyP₁₅₀ ameliorates fatal sepsis by inhibiting expression of the cell adhesion molecule and the accumulation of leukocytes in the vascular endothelium, thereby suppressing the increase in vascular permeability. Our results in this study suggest that polyP₁₅₀ could be a candidate for novel sepsis treatments.

収録刊行物

• Fundamental Toxicological Sciences

  Fundamental Toxicological Sciences 8 (3), 89-96, 2021

  一般社団法人 日本毒性学会

キーワード

• Sepsis
• Inorganic polyphosphates
• Cecal ligation and puncture
• Vascular permeability

詳細情報

• CRID: 1390007359727787136
• NII論文ID: 130008068071
• DOI: 10.2131/fts.8.89
• ISSN: 2189115X
• Web Site: https://www.jstage.jst.go.jp/article/fts/8/3/8_89/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2022159286
• 本文言語コード: en
• データソース種別:
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  • Crossref
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