Distribution of calcineurin activity in blood cell fractions and impact of tacrolimus inhibition.
The aim of this study was to investigate calcineurin (PP2B) activity in different blood cell fractions and its inhibition by tacrolimus. Basal PP2B activity was measured in each blood cellular fraction collected from healthy volunteers. The inhibition profile of PP2B activity was explored in isolated peripheral blood mononuclear cells (PBMC) and platelets exposed directly to tacrolimus and in PBMC and platelets isolated from whole blood previously exposed to tacrolimus. Contrasting with red blood cells (30%) and platelets (25%), PBMC represented only 8.7% of PP2B activity of unfractionated whole blood. After tacrolimus exposure of isolated PBMC and platelets, the concentration of tacrolimus required to inhibit 50% of PP2B activity (EC(50)) in PBMC was significantly lower than in platelets (0.26 ng/mL vs. 0.83 ng/mL, P < 0.001). EC(50) values were similar in PBMC and platelets isolated from whole blood previously exposed to tacrolimus (7.69 ng/mL vs. 7.42 ng/mL, respectively). These results suggest PBMC is a very suitable matrix for PP2B measurement in monitoring transplant recipients but clinical studies are necessary to solve clearly this issue.
Blanchet
Benoit
B
Laboratory of Pharmacology and Toxicology, Centre Hospitalier Universitaire Henri Mondor, 51, avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France.
Hulin
Anne
A
Ghaleh
Bijan
B
Giraudier
Stéphane
S
Jouault
Hélène
H
Astier
Alain
A
D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D019703:Calcineurin / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D019703:Calcineurin; D016559:Tacrolimus