Renal ischemia-reperfusion injury: new implications of dendritic cell-endothelial cell interactions.
In renal ischemia/reperfusion (I/R) injury endothelial cells are a main target. The disturbance of endothelial cell physiology leads to endothelial swelling and narrowing of the blood vessel lumen. We attribute this effect to impairment of endothelial cell nitric oxide synthase (NOS). NO is significantly reduced in the course of hypoxia causing dysfunction of the vascular smooth muscle tone. Subsequently to an I/R injury, the inflammatory response results in endothelial activation with enhanced dendritic cell (DC) adhesion and migration. Thus, alloreactive leukocytes are recruited to the inflammatory site. Finally, dendritic cell-endothelial cell interactions may play a crucial role in antigen-specific allograft rejection in I/R renal injury. DCs, which activate naïve alloreactive T cells, play a central role in the establishment of alloantigen-specific immunity. In the course of hypoxia rejection is initiated at the activated layer of foreign endothelial cells (EC), which forms an immunogenic barrier for migrating DCs and T cells. Host DCs that bind to postischemic activated ECs invade the allografted tissues, or remain stationary in the subendothelial layer, or transmigrate into lymphoid vessels and secondary lymphoid organs, where they present alloantigens to naïve host T cells. Organ rejection is mediated by host alloreactive T cells, which are activated by donor DCs (direct activation) or host DCs (indirect activation). We hypothesized that DC-EC binding and migration is the first step in the renal I/R injury that mediates allotransplant rejection. We sought to better understand the downstream events of a renal I/R injury by understanding DC binding and migration, thereby seeking new strategies for more specific immunomodulatory interventions. Herein we developed a new allotransplant-rejection model after renal I/R injury.
Schlichting
C L
CL
Department of Surgery, Division of Transplantation Surgery, School of Medicine, University Hospital, University Rostock, Rostock, Germany. christoph.schlichting@drschlichting.de
Schareck
W D
WD
Weis
M
M
D000938:Antigen-Presenting Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology