TY  - JOUR
AB  - 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.
AU  - Chakraborty, Deblina
AU  - Zenker, Stefanie
AU  - Rossaint, Jan
AU  - Hölscher, Anna
AU  - Pohlen, Michéle Yvonne
AU  - Pohlen, Michéle
AU  - Zarbock, Alexander
AU  - Roth, Johannes
AU  - Vogl, Thomas
DA  - 2017-11-13
DO  - 10.3389/fimmu.2017.01493
KW  - damage-associated molecular patterns
KW  - S100A8
KW  - TLR4
KW  - type I alveolar epithelial cells
KW  - type II alveolar epithelial cells
KW  - IL-6
KW  - neutrophils
LA  - eng
N1  - Frontiers in Immunology 8 (2017) 1493, 1-16
N1  - Finanziert durch den Open-Access-Publikationsfonds 2017 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2017-11-13
TI  - Alarmin S100A8 Activates Alveolar Epithelial Cells in the Context of Acute Lung Injury in a TLR4-Dependent Manner
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-15169619444
Y2  - 2024-11-24T21:07:26
ER  -