Angiostatin inhibits acute lung injury in a mouse model

Acute lung injury is marked by profound influx of activated neutrophils, which have delayed apoptosis, along with fluid accumulation that impairs lung function and causes high mortality. Inflammatory and antimicrobial molecules, such as reactive oxygen species from activated neutrophils with prolonged lifespan, cause tissue damage and contribute to lung dysfunction. Angiostatin, an endogenous antiangiogenic molecule, is expressed in the lavage fluid of patients with acute respiratory distress syndrome and modifies neutrophil infiltration in a mouse model of peritonitis. Our aim was to investigate the therapeutic role of angiostatin in acute lung injury. We analyzed bronchoalveolar lavage and lung tissues from C57BL/6 mouse model of Escherichia coli LPS-induced acute lung injury to assess the effects of angiostatin treatment. Subcutaneous angiostatin administered at 5 h after LPS treatment reduces histological signs of inflammation, protein accumulation, lung Gr1+ neutrophils, myeloperoxidase activity, and expression of phosphorylated p38 MAPK in lung tissues and peripheral blood neutrophils, while increasing the number of apoptotic cells in the lungs without affecting the levels of macrophage inflammatory protein-1 α, IL-1β, keratinocyte chemoattractant, and monocyte chemoattractant protein-1 in lavage and lung homogenates at 9 and 24 h after LPS treatment. In contrast, angiostatin administered intravenously 5 h after LPS treatment did not reduce histological sign of inflammation, BAL cell recruitment, and protein concentration at 9 h of LPS treatment. We conclude that angiostatin administered subcutaneously after LPS challenge inhibits acute lung inflammation up to 24 h after LPS treatment.