University of Lille, U1019, UMR 8204, Center for Infection and Immunity of Lille, Lille, France.
Centre National de la Recherche Scientifique, UMR 8204, Lille, France.
J Appl Physiol (1985). 2019 Sep 1;127(3):668-678. doi: 10.1152/japplphysiol.00337.2019. Epub 2019 Jul 11.
Acute respiratory distress syndrome is a severe form of respiratory failure, occurring in up to 20% of patients admitted to the intensive care unit with sepsis. Dysregulated leukocyte diapedesis is a major contributor to acute respiratory distress syndrome. Endocan is a circulating proteoglycan that binds to the leukocyte integrin leukocyte functional antigen-1 and blocks its interaction with its endothelial ligand, ICAM-1. The objective of this study was to evaluate the role of endocan in the control of acute lung inflammation. In vitro, endocan inhibited human leukocyte transendothelial migration as well as ICAM-1-dependent migration but had a very mild effect on ICAM-1-dependent adhesion. Endocan also acted as an inhibitor of transendothelial migration of mouse leukocytes. The effect of systemic administration of recombinant human endocan was assessed in a model of acute lung inflammation in BALB/c mice. Treatment with endocan 1 h after intratracheal LPS challenge reduced the alveolar inflammatory response, diminished histological features of acute lung injury, and improved respiratory function. These results highlight the anti-inflammatory role of human endocan and its protective effect against acute lung injury. We show here that endocan inhibits ICAM-1-dependent human leukocyte transendothelial migration and ICAM-1-dependent adhesion. We also found that in BALB/c mice with tracheal LPS-induced acute lung injury treatment with recombinant human endocan reduces lung inflammation, notably through reduction of neutrophilic recruitment, and restores normal lung function. These results confirm the hypothesis that human endocan may have a protective effect against acute lung inflammation.
急性呼吸窘迫综合征是一种严重的呼吸衰竭形式，在入住重症监护病房的败血症患者中，其发病率高达 20%。白细胞渗出失调是急性呼吸窘迫综合征的主要原因之一。内脂素是一种循环蛋白聚糖，可与白细胞整合素白细胞功能抗原-1 结合，并阻断其与内皮配体 ICAM-1 的相互作用。本研究的目的是评估内脂素在控制急性肺炎症中的作用。在体外，内脂素抑制人白细胞穿过内皮迁移以及 ICAM-1 依赖性迁移，但对 ICAM-1 依赖性黏附的影响非常轻微。内脂素还可作为小鼠白细胞穿过内皮迁移的抑制剂。通过在 BALB/c 小鼠急性肺炎症模型中评估重组人内脂素的系统给药作用来评估内脂素的作用。在气管内 LPS 挑战后 1 小时给予内脂素治疗可减轻肺泡炎症反应，减轻急性肺损伤的组织学特征，并改善呼吸功能。这些结果强调了人内脂素的抗炎作用及其对急性肺损伤的保护作用。我们在这里表明，内脂素抑制 ICAM-1 依赖性人白细胞穿过内皮迁移和 ICAM-1 依赖性黏附。我们还发现，在气管内 LPS 诱导的 BALB/c 小鼠急性肺损伤中，重组人内脂素治疗可减少肺炎症，特别是通过减少中性粒细胞募集，并恢复正常的肺功能。这些结果证实了人内脂素可能对急性肺炎症具有保护作用的假设。
