The role of endothelial cells in the pathophysiology of sepsis has received increased attention since the publication of studies showing that activated protein C can improve survival in selected patients with sepsis. A recurring theme in sepsis research has been that the endothelial cells can drive the inflammatory response by release of procoagulant and proinflammatory molecules. It is now clear that there is “cross-talk” between the coagulation and inflammatory cascades. Thus, prevention of endothelial injury and the resultant intravascular coagulation may modulate the production of proinflammatory cytokines and chemokines.

Based on this hypothesis, investigators have examined endothelial injury and death using various models of sepsis and infection. Numerous studies have demonstrated that endothelial cells undergo apoptosis in response to a host of stimuli including serum growth factor withdrawal, Fas activation, and radiation injury (1–4). Apoptosis of endothelial cells also has been reported in regions of atherosclerotic plaques. Considered together, these studies show that endothelial cells are capable of undergoing apoptosis in response to certain stimuli. Similarly, in vitro infectious models demonstrated that certain organisms induce endothelial cell apoptosis. Haemophilus somnus, a common cause of pneumonia and vasculitis in cattle, causes apoptosis in bovine endothelial cells in vitro (5). Staphylococcus aureus can be ingested by human umbilical vein endothelial cells, and uptake of the bacteria induces apoptosis in the infected cells (6).