Physiological roles for ecto-5’-nucleotidase (CD73)

Nucleotides and nucleosides influence nearly every aspect of physiology and pathophysiology. Extracellular nucleotides are metabolized through regulated phosphohydrolysis by a series of ecto-nucleotidases. The formation of extracellular adenosine from adenosine 5’-monophosphate is accomplished primarily through ecto-5’-nucleotidase (CD73), a glycosyl phosphatidylinositol-linked membrane protein found on the surface of a variety of cell types. Recent in vivo studies implicating CD73 in a number of tissue protective mechanisms have provided new insight into its regulation and function and have generated considerable interest. Here, we review contributions of CD73 to cell and tissue stress responses, with a particular emphasis on physiologic responses to regulated CD73 expression and function, as well as new findings utilizing Cd73-deficient animals

Vascular pathophysiology of cytomegalovirus infection after kidney transplantation

The endothelium is one of the tissues that can become infected during cytomegalovirus (CMV) infection. Because of its location and function endothelium plays a crucial role in the dissemination and pathophysiology of the virus. In the present thesis a series of studies is described concerning to the role of endothelium during CMV inection is described. In these studies, kidney transplant recipients were monitored for CMV infection and during the infection several parameters related to vascular damage were studied and related to acute rejection episodes.... Zie: Summary

Donor-derived circulating endothelial cells after kidney transplantation

Background. In solid-organ transplantation, the allograft vasculature, in particular the endothelium, is prone to injury inflicted by peritransplantational and posttransplantational factors. Previously, we have shown that circulating endothelial cells (cEC) can be detected in the peripheral blood of kidney allograft recipients and are often associated with acute rejection and active infections with human cytomegalovirus. In the present study we hypothesized that cEC after kidney transplantation are of donor origin, thus reflecting transplantation-related damage to the allograft endothelium. Methods. Using hydraulic micromanipulation equipment, we isolated single cEC (n=153) from the peripheral blood of nine kidney allograft recipients at various time points after transplantation. We demonstrated the origin of these cells (donor or recipient) by typing their HILA-DRB alleles by single-cell, genomic, nested polymerase chain reaction. Results. The majority (71.8%) of cEC were of donor origin and could be detected up to 141 days after onset of acute rejection episodes. Although less frequent (28.2%), recipient-type cEC were detected in the same time course as donor-type cEC. Conclusion. We conclude that posttransplantational injury to the allograft endothelium is reflected by the presence of donor-derived cEC in the blood

Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection:Effect of acute rejection

After transplantation, human cytomegalovirus (HCMV) infections can cause vascular damage to both the graft and the host. To study a possible relationship between the degree of vascular injury, clinical symptoms of HCMV infection, and transplant rejection, the appearance and numbers of endothelial cells (ECs) in blood of 54 kidney transplant recipients were investigated in a prospective clinical study. Two types of endothelial cells were identified: cytomegalic ECs (CECs) were detected in patients with moderate or high HCMV antigenemia, and uninfected ECs were observed in patients with and without HCMV infection. The incidence of either CECs, ECs, or the combination of both was associated with HCMV-related clinical symptoms (P</p