A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells.
Vascular endothelial cells regulate the passage of fluids, solutes, and cells from the vascular space to the tissues. Disruption of vascular integrity is involved in the pathogenesis of inflammatory diseases including transfusionrelated acute lung injury (TRALI), a most severe nonhemolytic transfusion reaction with symptoms such as dyspnea and/or hypotension and fever. Pulmonary edema, due to increased vascular permeability for macromolecules and plasma, is a hallmark of TRALI. The mortality rate of TRALI ranges from 5 to 10%. While donor antibodies (Abs) against human leukocyte antigen (HLA) class I and granulocytes are regarded as causative factors, various clinical studies have demonstrated the roles of anti-HLA class II-Ab on the etiology of TRALI, although the detailed mechanisms have not been clarified. Over several years we have investigated to clarify the underlying mechanism by which anti-HLA class II Abs cause an increase in endothelial permeability. In this review, we show that anti-HLA class II Ab generates proinflammatory cytokines and chemokines from HLA class II positive mononuclear cells of peripheral blood in an Fc R-dependent manner. As a result, the produced interleukin-1 and tumor necrosis factorlead to increased endothelial permeability via the nuclear factorB pathway but not apoptosis of endothelial cells. These findings provide a better understanding of the roles of anti-HLA class II Ab in the etiology of TRALI.