Functional Blockage of S100A8/A9 Ameliorates Ischemia–Reperfusion Injury in the Lung

Kentaro Nakata, Mikio Okazaki, Tomohisa Sakaue, Rie Kinoshita, Yuhei Komoda, Dai Shimizu, Haruchika Yamamoto, Shin Tanaka, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Hiromasa Yamamoto, Toshiaki Ohara, Seiichiro Sugimoto, Masaomi Yamane, Akihiro Matsukawa, Masakiyo Sakaguchi, Shinichi Toyooka

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


(1) Background: Lung ischemia–reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury.

Original languageEnglish
Article number673
Issue number11
Publication statusPublished - Nov 2022


  • damage-associated molecule patterns
  • ischemia reperfusion injury
  • lung transplantation
  • S100A8/A9

ASJC Scopus subject areas

  • Bioengineering


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