MDR1 gene expression in peripheral blood mononuclear cells after liver transplantation.
BACKGROUND
The multidrug resistance pump, P-glycoprotein 170 (P-gp), the MDR1 gene expression product, is expressed in peripheral blood mononuclear cells (PBMC). Cyclosporine (CsA) and tacrolimus are inhibitors and substrates of the pump, and can induce its expression. The aim of the present study was to assess MDR1 gene expression in PBMC after liver transplantation.


METHODS
P-gp expression was examined in PBMC from 23 adult patients by flow cytometry analysis using UIC2, a monoclonal anti-Pgp antibody, on days 7, 14, 21, 28, 90, and 180, and whenever a rejection episode was suspected. MDR1 mRNA was estimated by reverse transcription-polymerase chain reaction.


RESULTS
P-gp expression, assessed as the ratio of the mean fluorescence, increased from 1.59 before transplantation to 2.05 after transplantation, and did not vary significantly thereafter. There was no significant difference in P-gp expression between CsA and tacrolimus-based treatments. MDR1 mRNA levels did not vary significantly under CsA or tacrolimus therapy until day 28. P-gp expression was marginally higher in patients before acute rejection (P=0.054), and was lower in patients with severe infection (P=0.003) than in those with uneventful evolution. Alcoholic patients exhibited higher levels of P-gp expression than other patients.


CONCLUSIONS
P-gp expression increases after liver transplantation. Its variations do not allow the ability to predict acute rejection, but could help in making the diagnosis of overimmunosuppression.
Grudé
Pascale
P
Laboratoire de Biologie Cellulaire, Faculte de Medecine Cochin-Port Royal, Universite Paris V, 75014 Paris, France.
Boleslawski
Emmanuel
E
Conti
Filomena
F
Chouzenoux
Sandrine
S
Calmus
Yvon
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D017252:CD3 Complex / Q000032:analysis; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000502:physiology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D016559:Tacrolimus / Q000008:administration & dosage
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; D016559:Tacrolimus