Speaker
Description
Acute lung injury (ALI) is a heterogeneous lung injury characterised by infiltration of phagocytes in the lungs. Alveolar epithelial cells (AECs) are an essential part of the respiratory barrier in lungs for gas exchange and protection against pathogens. During ALI the alveolar capillary barrier, which is made of the epithelial layer and the endothelial layer, is disrupted. Endogenous Damage Associated Molecular Pattern Molecules (DAMPs) and Pathogen Associated Molecular Pattern molecules (PAMPs) activate the epithelial and endothelial cells to release cytokines and chemokines leading to ALI. However, their interplay as well as the mechanism of AECs’ activation especially by the alarmin S100A8 is unknown. During the barrier breakdown phagocytes migrate into the lung to eliminate the infection. Thus, our aim was to study the mechanism of activation of AECs (type I and type II) by S100A8 or lipopolysaccharide (LPS) and to understand the role of endogenous S100A8 in phagocytes recruitment in the lung. We here clearly demonstrate that AEC s are activated by S100A8 via a TLR4-dependent pathway whereas RAGE, albeit mainly expressed in lung tissue, does not play a role. Additionally, we show that S100A8 is an essential factor for neutrophil recruitment to lungs and the stimulation of all the recruited phagocytes.
