Adenovirus-Delivered Angiopoietin 1 Accelerates the Resolution of Inflammation of Acute Endotoxic Lung Injury in Mice

作者：Xu, You-Nian; Zhang, Zhao; Ma, Pu; Zhang, Shi-Hai^*

来源：Anesthesia and Analgesia, 2011, 112(6): 1403-1410.

DOI：10.1213/ANE.0b013e318213fbd3

• COLONY-STIMULATING FACTOR
• RESPIRATORY-DISTRESS-SYNDROME
• NF-KAPPA-B
• NEUTROPHIL APOPTOSIS
• ACTIVATION
• PATHWAYS
• TRANSMIGRATION
• PHAGOCYTOSIS
• INHIBITION
• MODULATION

BACKGROUND: The immune system plays a key role in protecting the organism from infection. Timely resolution of the inflammatory response to infection plays a vital role in returning homeostasis and maintaining normal organ function. Angiopoietin1 prevents endothelial activation, part of the inflammatory response to a pathogen, and has an anti-inflammatory effect in acute lung injury. We designed this study to investigate whether increasing serum production of angiopoietin1 by IV administration of adenoviral-delivered angiopoietin1 could accelerate the resolution of inflammation in endotoxin-induced acute lung injury in mice.
METHODS: Lipopolysaccharide was intratracheally instilled to induce acute lung injury in animals pretreated for 24 hours with adenoviral-GFP vector or adenoviral-GFP-angiopoietin1, respectively. An additional 6 mice in each pretreatment group were killed before lipopolysaccharide instillation to serve as controls. Indices of resolution of inflammation were analyzed. Apoptotic polymorphonuclear leukocytes and their phagocytosis by macrophages were determined by fluorescent activated cell sorter. The expression of angiopoietin1 in tissues and granulocyte macrophage colony-stimulating factor in the bronchoalveolar lavage fluid were measured.
RESULTS: Lipopolysaccharide induced leukocyte infiltration into air spaces, with maximal infiltration 48 hours after lipopolysaccharide instillation. Pretreatment with adenovirus-GFP-angiopoietin1 markedly increased angiopoietin1 expression, reduced leukocyte, and neutrophil infiltration and shortened the duration of inflammation. Adenovirus-GFP-angiopoietin1 pretreatment augmented the magnitude without altering the time course of granulocyte macrophage colony-stimulating factor.
CONCLUSIONS: Our results suggest that angiopoietin1 pretreatment promotes resolution of inflammation in endotoxin-induced acute lung injury in mice by accelerating the apoptosis of neutrophils and their phagocytosis by macrophages. (Anesth Analg 2011; 112: 1403-10)

• 出版日期2011-6
• 单位华中科技大学