ReviewROS-activated calcium signaling mechanisms regulating endothelial barrier function

- Increased reactive oxygen species (ROS) generated in tissue during inflammation play an important role in the development of ALI and its progression to ARDS.
- ROS initiated Ca2+ signaling in tissue plays an important role in increasing endothelial permeability.
- Redox sensitive TRPM2 channel and TRPC6 and other TRPCs such as TRPC1 which form CRAC by connecting with ORAI and ROS sensor STIM1, are key players in mediating ROS-induced Ca2+ signaling in regulating endothelial permeability upon oxidant stress.

Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI.