Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wygrecka, M; Kosanovic, D; Wujak, L; Reppe, K; Henneke, I; Frey, H; Didiasova, M; Kwapiszewska, G; Marsh, LM; Baal, N; Hackstein, H; Zakrzewicz, D; Müller-Redetzky, HC; de Maat, S; Maas, C; Nolte, MW; Panousis, C; Schermuly, RT; Seeger, W; Witzenrath, M; Schaefer, L; Markart, P.
Antihistone Properties of C1 Esterase Inhibitor Protect against Lung Injury.
Am J Respir Crit Care Med. 2017; 196(2):186-199
Doi: 10.1164/rccm.201604-0712OC
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Kwapiszewska-Marsh Grazyna
- Marsh Leigh
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bronchoalveolar Lavage Fluid -
- Complement C1 Inhibitor Protein - metabolism
- Complement C1 Inhibitor Protein - pharmacology
- Disease Models, Animal -
- Histones - metabolism
- Humans -
- Lung - metabolism
- Lung - physiopathology
- Lung Injury - physiopathology
- Lung Injury - prevention & control
- Mice -
- Mice, Inbred C57BL -
- Respiratory Distress Syndrome, Adult - physiopathology
- Find related publications in this database (Keywords)
- ARDS
- cell death
- extracellular histones
- C1 esterase inhibitor