We describe enhanced expression and enzymatic activity of ecto-ATPase and ecto-5P Pnucleotidase on CMV infected endothelial cells as compared to uninfected cells. These ectoenzymes play a major role in modulation of platelet activation and aggregation. Furthermore, adenosine has a modulatory effect upon inflammation. Addition of ATP, ADP or AMP to cultures of CMV infected or uninfected endothelial cells revealed increased turnover of AMP in CMV infected endothelial cells. In addition, the superoxide production by stimulated polymorphonuclear cells was inhibited in the presence of CMV infected endothelial cells as compared to uninfected cells, probably due to the enhanced activity of ecto-5P Pnucleotidase and associated to production of adenosine. ß

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<.01). Remarkably, the occurrence of rejection episodes before HCMV infection was an important risk factor for the occurrence of ECs in blood (ECs, CECs, or both) during HCMV infection (P<.001).

CMV infection is associated with vascular damage, and the vascular damage during CMV infection is enhanced if patients experienced acute rejection before CMV infection.

Objective: The cytomegalovirus (CMV) antigenemia consists of the detection of CMV pp65 in the nucleus of polymorphonuclear granulocytes (PMN), but it is unclear where and how PMN pick up virus particles or proteins. In an in vitro model for CMV antigenemia we investigated the mechanism of pp65 uptake by PMN that results in its expression in the nucleus. Methods: A series of inhibitors of different mechanisms was used to study the uptake of pp65 by PMN during coculture with CMV-infected endothelial cells and we performed a morphological analysis by light and transmission electron microscopy. Results: Nocodazole and cytochalasin B inhibited uptake of pp65 by PMN with 59.4 ± 14.1 and 73.3 ± 12.7%, respectively. The presence of anti-CMV hyperimmune globulin or lactoferrin during coculture reduced the number of pp65-positive PMN with 45.8 ± 7.0 or 40.6 ± 3.2%. Furthermore, a small number of the pp65-positive PMN obtained after coculture had fused to large cells with multilobed nuclei. PMN were observed that enclosed viral particles as well as free viral particles containing PMN in the cytoplasm. Conclusion: Fusion of viral particles with PMN and phagocytosis are both involved in the uptake of pp65.

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