Antihistone Properties of C1 Esterase Inhibitor Protect against Lung Injury.
Am J Respir Crit Care Med
; 196(2): 186-199, 2017 07 15.
Article
en En
| MEDLINE
| ID: mdl-28005404
ABSTRACT
RATIONALE Acute respiratory distress syndrome is characterized by alveolar epithelial cell injury, edema formation, and intraalveolar contact phase activation. OBJECTIVES:
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.METHODS:
The ability of C1INH to control the inflammatory processes was studied in vitro and in vivo. MEASUREMENTS AND MAINRESULTS:
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.CONCLUSIONS:
Collectively, C1INH administration provides a new therapeutic option for disorders associated with histone release.Palabras clave
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1
Banco de datos:
MEDLINE
Asunto principal:
Síndrome de Dificultad Respiratoria
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Histonas
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Proteína Inhibidora del Complemento C1
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Lesión Pulmonar
Límite:
Animals
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Humans
Idioma:
En
Revista:
Am J Respir Crit Care Med
Asunto de la revista:
TERAPIA INTENSIVA
Año:
2017
Tipo del documento:
Article