Antihistone Properties of C1 Esterase Inhibitor Protect against Lung Injury
| Autor: | Nelli Baal, Ingrid Henneke, Grazyna Kwapiszewska, Leigh M. Marsh, Holger Hackstein, Dariusz Zakrzewicz, Marc W. Nolte, de Maat S, Martin Witzenrath, Malgorzata Wygrecka, Ralph T. Schermuly, Werner Seeger, Con Panousis, P. Markart, Lukasz Wujak, Katrin Reppe, Djuro Kosanovic, Miroslava Didiasova, Holger Müller-Redetzky, Helena Frey, Liliana Schaefer, Coen Maas |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Programmed cell death ARDS Endogeny 030204 cardiovascular system & hematology Lung injury Critical Care and Intensive Care Medicine Histones Mice 03 medical and health sciences 0302 clinical medicine In vivo Extracellular Animals Humans Medicine Lung Respiratory Distress Syndrome biology business.industry Lung Injury medicine.disease Molecular biology In vitro Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology Histone biology.protein business Bronchoalveolar Lavage Fluid Complement C1 Inhibitor Protein |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 196:186-199 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.201604-0712oc |
| Popis: | Acute respiratory distress syndrome is characterized by alveolar epithelial cell injury, edema formation, and intraalveolar contact phase activation.To explore whether C1 esterase inhibitor (C1INH), an endogenous inhibitor of the contact phase, may protect from lung injury in vivo and to decipher the possible underlying mechanisms mediating protection.The ability of C1INH to control the inflammatory processes was studied in vitro and in vivo.Here, we demonstrate that application of C1INH alleviates bleomycin-induced lung injury via direct interaction with extracellular histones. In vitro, C1INH was found to bind all histone types. Interaction with histones was independent of its protease inhibitory activity, as demonstrated by the use of reactive-center-cleaved C1INH, but dependent on its glycosylation status. C1INH sialylated-N- and -O-glycans were not only essential for its interaction with histones but also to protect against histone-induced cell death. In vivo, histone-C1INH complexes were detected in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome and multiple models of lung injury. Furthermore, reactive-center-cleaved C1INH attenuated pulmonary damage evoked by intravenous histone instillation.Collectively, C1INH administration provides a new therapeutic option for disorders associated with histone release. |
| Databáze: | OpenAIRE |
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