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Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection.
Transpl Int. 2000; 13 Suppl 1:S324-8.TI

Abstract

The interaction between Fas and its ligand (FasL) induces apoptosis in the Fas-expressing cell. We hypothesized that liposome-mediated FasL gene transduction to the lung allograft, in addition to low-dose immunosuppression, might reduce acute rejection. Orthotopic left lung allotransplantation was performed in male rats (Brown Norway to Fischer F344). FasL gene transfer was performed by use of the plasmid pBCMGSNeo carrying the gene coding for murine FasL and the cationic liposome GL#67:DOPE. Six hundred and sixty micrograms of DNA in 250 microl H2O and 0.5 micromol GL#67 in 250 microl H2O were diluted to 5 ml with saline solution. This emulsion (20 degrees C) was instilled retrogradely through the left pulmonary vein after flushing with LPD solution (20 ml, at 4 degrees C). Subsequently, the graft was stored at 10 degrees C for 3 h. A single dose of cyclosporine A (CsA; 2.5 mg/kg i.m.) was given to all groups 48 h after the transplantation. In group 1 (n = 6), FasL/GL#67 was instilled as described. In group 2 (n = 5), GL#67 was given without DNA. Group 3 (n = 5) animals received CsA only. Five days after transplantation, gas exchange was assessed after exclusion of the contralateral native lung (FiO2 = 1.0). Grafts were flushed with saline solution and fixed in formaldehyde for histological evaluation. No statistical difference in gas exchange (PaO2) between the two control groups 2 (6.4 +/- 0.4 kPa) and 3 (7.4 +/- 0.4 kPa) could be detected 5 days postoperatively (P = 0.9). In contrast, grafts transduced with FasL (group 1) had significantly better gas exchange on postoperative day 5 (PaO2: group 1 37.0 +/- 10.6 kPa vs group 2 6.4 +/- 0.41 kPa; P = 0.002). Two animals in group 1 revealed no or only minimal improvement in gas exchange. Histologically, all lung specimen of all groups showed signs of acute rejection (A2). Leukocyte infiltrates, rated by two independent observers, were less severe in all group 1 animals. Liposome-mediated FasL gene transfer at the time of harvest in combination with low-dose CsA reduces acute rejection in four out of six animals in this model of rat lung allotransplantation.

Authors+Show Affiliations

Department of Medicine, University Hospital Zurich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11112024

Citation

Schmid, R A., et al. "Fas Ligand Gene Transfer Combined With Low Dose Cyclosporine a Reduces Acute Lung Allograft Rejection." Transplant International : Official Journal of the European Society for Organ Transplantation, vol. 13 Suppl 1, 2000, pp. S324-8.
Schmid RA, Stammberger U, Hillinger S, et al. Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection. Transpl Int. 2000;13 Suppl 1:S324-8.
Schmid, R. A., Stammberger, U., Hillinger, S., Gaspert, A., Boasquevisque, C. H., Malipiero, U., Fontana, A., & Weder, W. (2000). Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection. Transplant International : Official Journal of the European Society for Organ Transplantation, 13 Suppl 1, S324-8.
Schmid RA, et al. Fas Ligand Gene Transfer Combined With Low Dose Cyclosporine a Reduces Acute Lung Allograft Rejection. Transpl Int. 2000;13 Suppl 1:S324-8. PubMed PMID: 11112024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection. AU - Schmid,R A, AU - Stammberger,U, AU - Hillinger,S, AU - Gaspert,A, AU - Boasquevisque,C H, AU - Malipiero,U, AU - Fontana,A, AU - Weder,W, PY - 2000/12/9/pubmed PY - 2001/6/2/medline PY - 2000/12/9/entrez SP - S324 EP - 8 JF - Transplant international : official journal of the European Society for Organ Transplantation JO - Transpl Int VL - 13 Suppl 1 N2 - The interaction between Fas and its ligand (FasL) induces apoptosis in the Fas-expressing cell. We hypothesized that liposome-mediated FasL gene transduction to the lung allograft, in addition to low-dose immunosuppression, might reduce acute rejection. Orthotopic left lung allotransplantation was performed in male rats (Brown Norway to Fischer F344). FasL gene transfer was performed by use of the plasmid pBCMGSNeo carrying the gene coding for murine FasL and the cationic liposome GL#67:DOPE. Six hundred and sixty micrograms of DNA in 250 microl H2O and 0.5 micromol GL#67 in 250 microl H2O were diluted to 5 ml with saline solution. This emulsion (20 degrees C) was instilled retrogradely through the left pulmonary vein after flushing with LPD solution (20 ml, at 4 degrees C). Subsequently, the graft was stored at 10 degrees C for 3 h. A single dose of cyclosporine A (CsA; 2.5 mg/kg i.m.) was given to all groups 48 h after the transplantation. In group 1 (n = 6), FasL/GL#67 was instilled as described. In group 2 (n = 5), GL#67 was given without DNA. Group 3 (n = 5) animals received CsA only. Five days after transplantation, gas exchange was assessed after exclusion of the contralateral native lung (FiO2 = 1.0). Grafts were flushed with saline solution and fixed in formaldehyde for histological evaluation. No statistical difference in gas exchange (PaO2) between the two control groups 2 (6.4 +/- 0.4 kPa) and 3 (7.4 +/- 0.4 kPa) could be detected 5 days postoperatively (P = 0.9). In contrast, grafts transduced with FasL (group 1) had significantly better gas exchange on postoperative day 5 (PaO2: group 1 37.0 +/- 10.6 kPa vs group 2 6.4 +/- 0.41 kPa; P = 0.002). Two animals in group 1 revealed no or only minimal improvement in gas exchange. Histologically, all lung specimen of all groups showed signs of acute rejection (A2). Leukocyte infiltrates, rated by two independent observers, were less severe in all group 1 animals. Liposome-mediated FasL gene transfer at the time of harvest in combination with low-dose CsA reduces acute rejection in four out of six animals in this model of rat lung allotransplantation. SN - 0934-0874 UR - https://www.unboundmedicine.com/medline/citation/11112024/Fas_ligand_gene_transfer_combined_with_low_dose_cyclosporine_A_reduces_acute_lung_allograft_rejection_ L2 - http://link.springer.com/article/10.1007/s001470050353 DB - PRIME DP - Unbound Medicine ER -