Alarmin S100A8 Activates Alveolar Epithelial Cells in the Context of Acute Lung Injury in a TLR4-Dependent Manner

Alveolar epithelial cells (AECs) are an essential part of the respiratory barrier in lungs for gas exchange and protection against pathogens. Damage to AECs occurs during lung injury and PAMPs/DAMPs have been shown to activate AECs. However, their interplay as well as the mechanism of AECs’ activati...

Verfasser: Chakraborty, Deblina
Zenker, Stefanie
Rossaint, Jan Peter
Hölscher, Anna
Pohlen, Michéle Yvonne
Zarbock, Alexander
Roth, Johannes
Vogl, Thomas
FB/Einrichtung:FB 05: Medizinische Fakultät
Dokumenttypen:Artikel
Medientypen:Text
Erscheinungsdatum:2017
Publikation in MIAMI:14.03.2019
Datum der letzten Änderung:12.01.2024
Angaben zur Ausgabe:[Electronic ed.]
Schlagwörter:damage-associated molecular patterns; S100A8; TLR4; type I alveolar epithelial cells; type II alveolar epithelial cells; IL-6; neutrophils
Fachgebiet (DDC):610: Medizin und Gesundheit
Lizenz:CC BY 4.0
Sprache:English
Anmerkungen:Frontiers in Immunology 8 (2017) 1493, 1-16
Förderung:Finanziert durch den Open-Access-Publikationsfonds 2017 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF-Dokument
URN:urn:nbn:de:hbz:6-15169619444
Weitere Identifikatoren:DOI: 10.3389/fimmu.2017.01493
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-15169619444
Onlinezugriff:artikel_vogl_2017.pdf

Alveolar epithelial cells (AECs) are an essential part of the respiratory barrier in lungs for gas exchange and protection against pathogens. Damage to AECs occurs during lung injury and PAMPs/DAMPs have been shown to activate AECs. However, their interplay as well as the mechanism of AECs’ activation especially by the alarmin S100A8/A9 is unknown. Thus, our aim was to study the mechanism of activation of AECs (type I and type II) by S100A8 and/or lipopolysaccharide (LPS) and to understand the role of endogenous S100A8/A9 in neutrophil recruitment in the lung. For our studies, we modified a previous protocol for isolation and culturing of murine AECs. Next, we stimulated the cells with S100A8 and/or LPS and analyzed cytokine/chemokine release. We also analyzed the contribution of the known S100-receptors TLR4 and RAGE in AEC activation. In a murine model of lung injury, we investigated the role of S100A8/A9 in neutrophil recruitment to lungs. S100A8 activates type I and type II cells in a dose- and time-dependent manner which could be quantified by the release of IL-6, KC, and MCP-1. We here clearly demonstrate that AEC s are activated by S100A8 via a TLR4-dependent pathway. Surprisingly, RAGE, albeit mainly expressed in lung tissue, plays no role. Additionally, we show that S100A8/A9 is an essential factor for neutrophil recruitment to lungs. We, therefore, conclude that S100A8 promotes acute lung injury via Toll-like receptor 4-dependent activation of AECs.