FIGURE 1.

Multifaceted role of vimentin in ARDS/ALI: Increased permeability of the alveolar-capillary membrane and pro-inflammatory conditions are fundamental characteristics of ALI. The schematic demonstrate very few epithelial cells due to increased cell death, and the intra-alveolar space depicted represents the alveolar lining fluid that is in contact with the air. The increased expression of surface vimentin on endothelial cells enhances lymphocyte adhesion and transmigration across endothelial cells through PSGL-1 binding on the lymphocytes, including neutrophils. Expression of vimentin and dynamics of Vimentin intermediate filaments regulate the endosomal signaling through Rab GTPase to transport VE-cadherin to the cell surface in endothelial cells for the maintenance of barrier functions. The PTM on vimentin in neutrophils leads to neutrophil extracellular traps (NETs) via netosis. NETs disrupt the microvascular endothelial barrier, increasing edematous and permeable vessels and causing a protein-rich fluid influx in the airspace. The increased expression of vimentin on platelets increases vitronectin and PAI-1 complex formation, which may provide stabilization of thrombi. The fibrins and fibrinolysis-related enzymes cause the dissolution of epithelial surface proteins and denudation of the epithelial barrier layer. Vimentin expression in fibroblasts regulates exocytosis and invasion, contributing to their proliferation in ALI. The surface vimentin on macrophage is essential for several bacteria and viruses for the host cell invasion and phagocytosis. Secreted vimentin from dead cell debris and activated immune cells act as DAMPs. The figure was created with BioRender.com.