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 FcγR-dependent manner.
As a result, the produced interleukin-1β and tumor necrosis factor-α lead to increased endothelial permeability via the nuclear
factor-κB 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.