Deferasirox, an iron-chelating agent, alleviates acute lung inflammation by inhibiting neutrophil activation and extracellular trap formation. Issue 9 (September 2020)

• Record Type: Journal Article
• Authors: Kono, Mari; Matsuhiroya, Shiori; Obuchi, Ayako; Takahashi, Takayuki; Imoto, Shion; Kawano, Seiji; Saigo, Katsuyasu
• Is Part Of: Journal of international medical research. Volume 48:Issue 9(2020)
• Publication Date: 2020-09
• Subjects: Neutrophil -- deferasirox -- neutrophil extracellular traps -- ALI model mouse -- acute lung injury -- reactive oxygen species; Medicine -- Periodicals; Pharmacology -- Periodicals; 610.5
• DOI: 10.1177/0300060520951015
• Languages: English
• ISSNs: 0300-0605

Abstract

Objective: Reactive oxygen species (ROS) production by neutrophils induces pulmonary endothelial cell damage and results in acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron-chelating agent, inhibits the ROS production and neutrophil extracellular trap (NET) formation induced by phorbol myristate acetate and formylmethionylleucylphenylalanine in vitro . In the present study, we investigated the effects of DFS in vivo using a mouse model of lipopolysaccharide (LPS)-induced ALI. Methods: After DFS administration for 7 days, ALI was induced in mice by LPS via intratracheal administration. Results: LPS treatment induced neutrophil invasion in the lung tissues, along with NET formation and a significant increase in the quantity of double-stranded DNA in the bronchoalveolar lavage fluid, while pre-administered DFS inhibited these phenomena. However, alteration of neutrophil morphology in the cytoplasm in terms of shape and vacuolization was not inhibited by the pre-administration of DFS, possibly through ROS production. Conclusions: DFS suppressed neutrophil invasion into lung tissues and reduced the double-stranded DNA content released by the neutrophils. These results suggest that DFS can potentially be used to prevent diseases related to neutrophil activation including ALI, thrombosis, and vascular endothelial dysfunction.