Augmentation of ischemia/reperfusion injury to endothelial cells by cyclosporin A.
Ischemia/reperfusion (I/R) carries significant injury to endothelial cells in transplanted organs and is an important factor in chronic rejection. Immunosuppressive drugs, notably cyclosporin A (CyA) and FK506, can potentially augment this injury. Here, our goal was to determine the combined effects of I/R and CyA or FK506 on endothelial cells. Transformed mouse endothelial cells (SVEC 4-10) were subjected to ischemia or I/R for 2-24 hours by incubating cells in 100 per cent N2 (ischemia) followed by 5 per cent CO2 and 95 per cent O2 (reperfusion) for 24 hours. In separate experiments, CyA or FK506 was added to cells subjected to ischemia or I/R. Nonviable cells were determined by Trypan blue exclusion assay. All experiments (done in triplicate) were analyzed by Student's t test. Increasing ischemia times resulted in a greater number of nonviable cells (2% nonviable cells at 0 hours and 57% at 24 hours of I/R). Addition of CyA significantly increased the number of nonviable cells when compared with the control (I/R only) group (P = 0.014). Interestingly, FK506 did not increase the percentage of nonviable cells compared with the control group (P = 0.2). Unlike FK506, CyA augments I/R injury to endothelial cells in vitro. These findings could be relevant in chronic rejection and transplantation.
Azizian
Maria
M
Department of Surgery, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Ramenaden
E Radhika
ER
Shah
Gaurang
G
Wilasrusmee
Chumpon
C
Bruch
David
D
Kittur
Dilip S
DS
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D065095:Calcineurin Inhibitors; D002452:Cell Count; D002461:Cell Line, Transformed; D002470:Cell Survival; D002478:Cells, Cultured / Q000187:drug effects; D004396:Coloring Agents; D016572:Cyclosporine / Q000009:adverse effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007511:Ischemia / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D051379:Mice; D009336:Necrosis; D015427:Reperfusion Injury / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D016559:Tacrolimus / Q000009:adverse effects*; D013997:Time Factors; D014343:Trypan Blue
D065095:Calcineurin Inhibitors; D004396:Coloring Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014343:Trypan Blue; D016559:Tacrolimus