Fas Ligand Gene Transfer to Renal Allografts in Rats

Swenson, Kim; Ke, Bibo; Wang, Tao; Markowitz, Jay S.; Maggard, Melinda A.; Spear, Gerald S.; Imagawa, David K.; Goss, John A.; Busuttil, Ronald W.; Seu, Philip

doi:10.1097/00007890-199801270-00002

Cited by 96 publications

(46 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Successful experimental results have been obtained using adenoviral IL-10, CTLA4-Ig, Fas Ligand and ICAM antisense to modulate the graft [58,59,60,611. Tolerance induction has been achieved in small animal studies by transfer of MHC Class I and I1 molecules However, whilst attractive and effective, at least in small animal models, several problems exist with these strategies.…”

Section: Genetic Modification Of Organs During Normothermic Preservationmentioning

confidence: 99%

Trends in organ preservation

McLaren

Friend

2003

Transplant International

View full text Add to dashboard Cite

Organ preservation aims to provide a viable graft with primary function post-transplant. The current basis of preservation for transplantation is static cold storage using specific preservation solutions which minimise cellular swelling and membrane pump activity, thus maintaining cellular ATP levels. The current organ shortage and consequent expansion of donor criteria places even greater reliance on minimising graft injury during preservation. This review focuses on current and future advances in preservation technology. The key areas of advance are additives to preservation solutions, alternatives/ adjuncts to preservation solutions including perfluorocarbons. A major area of advance is in the modulation of organs during the storage period. This may be achieved by biochemical additives or genetic manipulation. Machine perfusion technology is improving, and this is discussed together with the recent concept of warm (normothermic) perfusion as an alternative means of preservation. The authors provide an overview over the current methods of organ preservation. Cold storage, effective in the short-term is insufficient for marginal organs, does not allow assessment of viability markers, and provokes ischaemic injury. Potential strategies for minimising ischaemic injury include additives to preservation solutions; the two-layer method with perfluorcarbons and UW solution-at present limited to pancreas preservation; organ modulation; organ preconditioning and genetic modification of organs. In particular, the authors illuminate the potential in a reappraisal of the concept of normothermic perfusion.Keywords Transplantation . PreservationAbbreviations HSP Heat shock proteins . ICAM-I Intercellular adhesion molecule-1 . I/R Ischaemia reperfusion . PFC Perflurocarbon . U W University of Wisconsin solutionThe aims of presewation extended preservation times. This has provided important logistic benefits including, in the case of kidney The purpose of organ preservation in the context of transplantation, the institution of HLA-based organ transplantation is to deliver a viable graft to a recipient sharing across geographical boundaries. However there which will exhibit primary function. Improvements in is an increasing recognition that the limits of convenhypothermic preservation solutions have allowed tional preservation have been reached, and future

show abstract

Section: Genetic Modification Of Organs During Normothermic Preservationmentioning

confidence: 99%

Trends in organ preservation

McLaren

Friend

2003

Transplant International

View full text Add to dashboard Cite

show abstract

“…[19][20][21] Recently, a number of attempts have been made to deliver and express exogenous FasL in order to reduce the host immune responses to vector-transduced cells. [22][23][24][25][26] At the same time, a similar strategy was proposed to attack solid tumors and force their cells to undergo apoptosis. 27,28 Interestingly, in both cases, similar vectors were used, namely replication-defective adenoviral constructs with the FasL expression driven by a strong promoter such as the human cytomegalovirus immediateearly promoter/enhancer (CMVie).…”

Section: Introductionmentioning

confidence: 99%

Adenoviral vector which delivers FasL–GFP fusion protein regulated by the tet-inducible expression system

et al. 2000

View full text Add to dashboard Cite

Fas ligand (FasL) is a member of the tumor necrosis family and when bound to its receptor, Fas, induces apoptosis. It plays important roles in immune response, degenerative and lymphoproliferative diseases, development and tumorigenesis. It is also involved in generation of immune privilege sites in the eye and testis. Harnessing the power of this molecule is expected to lead to a powerful chemotherapeutic. We describe the construction and characterization of replication-deficient adenoviral vectors that express a fusion of murine FasL and green fluorescent protein (GFP). FasL-GFP retains full activity of wild-type FasL, at the same time allowing for easy visualization and quantification in both living and fixed cells. The fusion protein is under the control of a tetracycline-regulated gene expression system. Tight control of expression is achieved by creating a novel 'double

show abstract

“…Enforced expression of FasL has been shown to protect allografts from rejection in some cases (15,16) but not others (17). In the skin, tolerance induced by UV irradiation involves Fas/FasL (11,18) and a number of skin diseases are thought to involve FasL (19).…”

mentioning

confidence: 99%

Termination of Antigen-Specific Immunity by CD95 Ligand (Fas Ligand) and IL-10

Barreiro

Luker

Herndon

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Following elimination of a foreign invader, the immune system must return to its normal quiescent levels. This process requires removal of reactive immune cells when they are no longer needed. We have explored the role of Fas/Fas ligand (FasL) in terminating immunity and demonstrate that mice defective in these proteins have prolonged immune responses. Studies demonstrate that termination of immunity occurs via the interaction of Fas+ lymphoid cells with FasL+ nonlymphoid cells at the site of Ag challenge. Our results also show that FasL is absent in quiescent tissue but is rapidly up-regulated during the local immune reaction. This occurs through the production of IL-10. Thus, FasL and IL-10 work in concert to eliminate inflammatory cells and control the duration of an immune response.

show abstract

Fas Ligand Gene Transfer to Renal Allografts in Rats

Abstract: (1) Adenoviral vectors can successfully transduce rat kidneys with the FasL cDNA. (2) FasL gene transfer prolongs rat renal allograft survival.

Cited by 96 publications

References 24 publications

Trends in organ preservation

Trends in organ preservation

Adenoviral vector which delivers FasL–GFP fusion protein regulated by the tet-inducible expression system

Termination of Antigen-Specific Immunity by CD95 Ligand (Fas Ligand) and IL-10

Contact Info

Product

Resources

About