Experimental Approaches to Evaluate Leukocyte-Endothelial Cell Interactions in Sepsis and Inflammation.

Sepsis is a life-threatening syndrome of organ dysfunction caused by a dysregulated host response to infection characterized by excessive neutrophil infiltration into vital organs. In sepsis, patients often die of organ failure and therapies directed against endothelial cell dysfunction and tissue damage are important targets for treatment of this disease. Novel approaches are required to understand the underlying pathophysiology of neutrophil dysregulation and neutrophil-endothelial cell interactions that play a critical role in the early course of organ damage and disruption of endothelial protective barrier. Here, we review methodologies that our laboratories have employed to study neutrophil-endothelial interaction and endothelial barrier function in in vivo and in vitro models of sepsis. We will focus on in vivo rodent models of sepsis and in vitro tools that use human cell culture models under static conditions and the more physiologically relevant biomimetic microfluidic assays. This Methods paper is based on our presentation in the Master Class Symposium at the 41st Annual Conference on Shock 2018.