中性粒细胞胞外陷阱
急性呼吸窘迫综合征
血小板
促炎细胞因子
髓过氧化物酶
血小板活化
医学
炎症
药理学
中性粒细胞弹性蛋白酶
免疫学
肺
内科学
作者
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
出处
期刊:American Journal of Physiology-lung Cellular and Molecular Physiology
[American Physiological Society]
日期:2018-01-11
卷期号:314 (4): L654-L669
被引量:12
标识
DOI:10.1152/ajplung.00501.2016
摘要
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.
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