Temporal profile of calcineurin phosphatase activity during acute allograft rejection in the heterotopic rat heart transplantation model.
BACKGROUND
Regardless of the extensive worldwide use of calcineurin inhibitors, little is known about the behavior of calcineurin phosphatase (CaN) during acute allograft rejection. The aim of this study was to investigate the temporal profile of CaN during acute allograft rejection and reveal if it can be utilized as a pharmacodynamic marker to identify and monitor the rejection process.


METHODS
The heterotopic cervical rat heart transplantation model was used (dark Agouti to Lewis). We performed 25 control isogeneic and 46 allogeneic transplantations. Rats were sacrificed at various postoperative time points. CaN activity was measured in isolated peripheral blood and spleen mononuclear cells and in graft heart homogenates. CaN activity was measured as the release of radiolabeled phosphate from a previously phosphorylated 19 amino acid peptide.


RESULTS
We have shown that CaN's activity levels are not significantly altered during acute allograft rejection in peripheral blood mononuclear cells and in spleen-isolated mononuclear cells. CaN's intragraft activity decreased with time in both rejectors and controls, and was significantly lower in the allogeneic group.


CONCLUSIONS
CaN failed as a pharmacodynamic biomarker of acute allograft rejection in the heterotopic rat heart transplantation model. Further research is required in order to reveal the precise role of CaN during acute allograft rejection.
Karamperis
N
N
Research Laboratory C, Department of Renal Medicine C, Skejby, Aarhus University Hospital, Aarhus, Denmark. Karamperis@stofanet.dk
Koefoed-Nielsen
P B
PB
Marcussen
N
N
Ostraat
O
O
Jørgensen
K A
KA
D000818:Animals; D015415:Biomarkers / Q000097:blood; D006084:Graft Rejection / Q000201:enzymology* / Q000473:pathology; D006085:Graft Survival / Q000502:physiology; D016027:Heart Transplantation / Q000473:pathology*; D008214:Lymphocytes / Q000201:enzymology / Q000473:pathology; D009000:Monocytes / Q000201:enzymology / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic / Q000276:immunology
D015415:Biomarkers; C120817:calcineurin phosphatase; D010744:Phosphoric Monoester Hydrolases