Recombinant Antithrombin Attenuates Acute Respiratory Distress Syndrome in Experimental Endotoxemia

Haruka Okamoto, Isamu Muraki, Hideshi Okada*, Hiroyuki Tomita, Kodai Suzuki, Chihiro Takada, Yugo Wakayama, Ayumi Kuroda, Hirotsugu Fukuda, Yuki Kawasaki, Ayane Nishio, Maho Matsuo, Yuto Tamaoki, Risa Inagawa, Shigeo Takashima, Toshiaki Taniguchi, Akio Suzuki, Keiko Suzuki, Nagisa Miyazaki, Yoshinori KakinoRyu Yasuda, Tetsuya Fukuta, Yuichiro Kitagawa, Takahito Miyake, Tomoaki Doi, Takahiro Yoshida, Shozo Yoshida, Shinji Ogura

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

19 被引用数 (Scopus)

抄録

Sepsis-induced endothelial acute respiratory distress syndrome is related to microvascular endothelial dysfunction caused by endothelial glycocalyx disruption. Recently, recombinant antithrombin (rAT) was reported to protect the endothelial glycocalyx from septic vasculitis; however, the underlying mechanism remains unknown. Here, we investigated the effect of rAT administration on vascular endothelial injury under endotoxemia. Lipopolysaccharide (LPS; 20 mg/kg) was injected intraperitoneally into 10-week-old male C57BL/6 mice, and saline or rAT was administered intraperitoneally at 3 and 24 hours after LPS administration. Subsequently, serum and/or pulmonary tissues were examined for inflammation and cell proliferation and differentiation by histologic, ultrastructural, and microarray analyses. The survival rate was significantly higher in rAT-treated mice than in control mice 48 hours after LPS injection (75% versus 20%; P < 0.05). Serum interleukin-1β was increased but to a lesser extent in response to LPS injection in rAT-treated mice than in control mice. Lectin staining and ultrastructural studies showed a notable attenuation of injury to the endothelial glycocalyx after rAT treatment. Microarray analysis further showed an up-regulation of gene sets corresponding to DNA repair, such as genes involved in DNA helicase activity, regulation of telomere maintenance, DNA-dependent ATPase activity, and ciliary plasm, after rAT treatment. Thus, rAT treatment may promote DNA repair, attenuate inflammation, and promote ciliogenesis, thereby attenuating the acute respiratory distress syndrome caused by endothelial injury.

本文言語英語
ページ(範囲)1526-1536
ページ数11
ジャーナルAmerican Journal of Pathology
191
9
DOI
出版ステータス出版済み - 2021/09

ASJC Scopus 主題領域

  • 病理学および法医学

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