Osteopontin protects against lung injury caused by extracellular histones

Extracellular histones are present in the airways because of cell death occurring during inflammation. They promote inflammation and cause tissue damage due to their cationic nature. The anionic phosphoglycoprotein osteopontin (OPN) is expressed at high levels during airway inflammation and may neutralize the harmful activities of extracellular histones. During histone-induced acute lung injury, OPN–/– mice showed increased inflammation, extensive tissue injury, and high mortality compared to wild-type mice. In lipopolysaccharide-induced acute lung injury, wild-type mice showed less inflammation and tissue injury than OPN–/– mice. In bronchoalveolar lavage fluid from ARDS patients, high levels of OPN and also histone-OPN complexes were detected. In vitro, OPN bound to histones with high affinity, resulting in less cytotoxicity and reduced formation of tissue-damaging Neutrophil Extracellular Traps (NETs). The findings demonstrate that OPN can modulate the pro-inflammatory and cytotoxic properties of free histones, findings that may have therapeutic implications.

Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Kasetty, G., Papareddy, P., Bhongir, R. K., Ali, M., Mori, M., Wygrecka, M., Erjefält, J. S., Palmberg, L., Hultgardh, A., Herwald, H., Egesten, A. Tags: Mechanisms of Lung Injury and Repair Source Type: research