β-nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release

Yao Wen Chang, Ching Ping Tseng, Chih Hsun Lee, Tsong Long Hwang, Yu Li Chen, Mei Tzu Su, Kowit Yu Chong, Ying Wei Lan, Chin Chung Wu, Kung Ju Chen, Fen Hua Lu, Hsiang Ruei Liao, Chuen Hsueh, Pei Wen Hsieh

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. Emerging evidence indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increase acute inflammation and contribute to the development of ALI. Although numerous studies have increased our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, emphasizing that there is an urgent need for novel treatment strategies. In this study, a new series of small compounds of β-nitrostyrene derivatives (BNSDs) were synthesized, and their anti-inflammatory bioactivities on neutrophils and platelets were evaluated. The new small compound C7 modulates neutrophil function by inhibiting superoxide generation and elastase release. Compound C7 elicits protective effects on LPS-induced paw edema and acute lung injury via the inhibition of neutrophil accumulation, proinflammatory mediator release, platelet aggregation, myeloperoxidase activity, and neutrophil extracellular trap (NET) release. NET formation was identified as the bridge for the critical interactions between neutrophils and platelets by confocal microscopy and flow cytometry. This research provides new insights for elucidating the complicated regulation of neutrophils and platelets in ALI and sheds further light on future drug development strategies for ALI/ARDS and acute inflammatory diseases.

Original languageEnglish
Pages (from-to)L654-L669
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume314
Issue number4
DOIs
Publication statusPublished - 2018 Apr

Keywords

  • Acute lung injury
  • Lipopolysaccharide
  • Neutrophil extracellular trap
  • Neutrophil-platelet aggregates
  • β-nitrostyrene derivatives

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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