Academic Journal

The Actin-Binding Protein Cortactin Promotes Sepsis Severity by Supporting Excessive Neutrophil Infiltration into the Lung

التفاصيل البيبلوغرافية
العنوان: The Actin-Binding Protein Cortactin Promotes Sepsis Severity by Supporting Excessive Neutrophil Infiltration into the Lung
المؤلفون: Nathaniel L. Lartey, Hilda Vargas-Robles, Idaira M. Guerrero-Fonseca, Alexander García-Ponce, Citlaltepetl Salinas-Lara, Klemens Rottner, Michael Schnoor
المصدر: Biomedicines, Vol 10, Iss 5, p 1019 (2022)
بيانات النشر: MDPI AG, 2022.
سنة النشر: 2022
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: sepsis, acute lung injury, cytokine storm, actin-binding protein, cortactin, neutrophil diapedesis, Biology (General), QH301-705.5
الوصف: Sepsis is a systemic infection that can lead to multi-organ failure. It is characterised by an uncontrolled immune response with massive neutrophil influx into peripheral organs. Neutrophil extravasation into tissues depends on actin remodeling and actin-binding proteins such as cortactin, which is expressed ubiquitously, except for neutrophils. Endothelial cortactin is necessary for proper regulation of neutrophil transendothelial migration and recruitment to sites of infection. We therefore hypothesised that cortactin plays a crucial role in sepsis development by regulating neutrophil trafficking. Using a murine model of sepsis induced by cecal ligation and puncture (CLP), we showed that cortactin-deficient (KO) mice survive better due to reduced lung injury. Histopathological analysis of lungs from septic KO mice revealed absence of oedema, reduced vascular congestion and mucus deposition, and better-preserved alveoli compared to septic wild-type (WT) mice. Additionally, sepsis-induced cytokine storm, excessive neutrophil infiltration into the lung and oxidative stress were significantly reduced in KO mice. Neutrophil depletion 12 h after sepsis improved survival in WT mice by averting lung injury, similar to both neutrophil-depleted and non-depleted KO mice. Our findings highlight a critical role of cortactin for lung neutrophil infiltration and sepsis severity.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2227-9059
Relation: https://www.mdpi.com/2227-9059/10/5/1019; https://doaj.org/toc/2227-9059
DOI: 10.3390/biomedicines10051019
URL الوصول: https://doaj.org/article/1325b0d0be4b45629024edb6bc4fa0ca
رقم الانضمام: edsdoj.1325b0d0be4b45629024edb6bc4fa0ca
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22279059
DOI:10.3390/biomedicines10051019