My research focuses on leukocyte: vascular cell interactions affect endothelial cell-specific mediators, such as Angiopoietins (Ang) 1 & 2, and their role in the vascular dysfunction we observe in the development of acute lung injury (ALI). Under physiological conditions, expression of these 2 proteins and their interaction with their shared receptor, Tie2, is tightly regulated. However, in trauma patients and in our shock/sepsis mouse model for the development of ALI, Ang-2 in significantly up-regulated, deleteriously impacting vascular integrity (increased micro-vascular permeability and edema). Importantly, we have shown that significant aspect of this regulation of the Angiopoietins can be altered by interaction of pulmonary vascular EC and/or other vascular cells with activated neutrophils.
The aims of my project are to determine the kinetics of Ang-2/Ang-1 change in expression in response to insults like shock and/or sepsis and begin to unravel the mechanisms (cellular [leukocyte: vascular cell interactions] and/or molecular) that precipitate the loss of pulmonary vascular endothelial barrier function in the development of ALI.