Selective intra-graft apoptosis and down-regulation of lymphocyte bcl-2, iNOs and CD95L expression in kidney-pancreas transplanted patients after anti-Thymoglobulin induction.
Intra-graft infiltrating cells apoptosis was evaluated in 20 consecutive kidney-pancreas transplanted (KP) patients without kidney rejection. Two fine-needle aspirated biopsy (FNAB) and two peripheral blood lymphocytes (PBL) samples were obtained 14 days after transplantation. Immunosuppression was based on anti-Thymoglobulins (ATG) induction for 7 days and cyclosporine/mofetil mycophenolate as maintenance therapy. Ten matched healthy subjects were chosen as controls for PBL. Lymphocyte phenotypes and activation markers, apoptotic rate and lymphocyte expression of pro/anti-apoptotic molecules were analysed by flow cytometry analysis (FACS). Lymphocyte phenotypes and activation markers: higher levels of CD8 and CD4DR were evident in the graft (p < 0.05) than in PBL, CD3CD25 in PBL were higher in transplanted patients than in controls. Apoptotic rate and lymphocyte expression of pro- and anti-apoptotic molecules: a higher expression of annexin V, together with reduced lymphocytes CD95L, iNOs and Bcl-2 expression (PBL = 97.7+/-1.1% vs FNAB = 81.9+/-15.1%; p < 0.05) were evident in the graft than in PBL. In KP patients intra-graft apoptosis and reduced anti-apoptotic molecules were evident after ATG induction.
Fiorina
Paolo
P
Department of Internal Medicine I, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
Torriani
Gabriele
G
Gremizzi
Chiara
C
Davalli
Alberto M
AM
Orsenigo
Elena
E
Bruno Ventre
Marta
M
Dell'Antonio
Giacomo
G
Carlo
Valerio Di
VD
Rossini
Silvano
S
Secchi
Antonio
A
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D015536:Down-Regulation; D053222:Fas Ligand Protein; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology*; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D016035:Pancreas Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D000961:Antilymphocyte Serum; D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016572:Cyclosporine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D009173:Mycophenolic Acid