Blockade of very late antigen-4 integrin binding to fibronectin in allograft recipients. II. Treatment with connecting segment-1 peptides prevents chronic rejection by attenuating arteriosclerotic development and suppressing intragraft T cell and macrophage activation

Transplantation
S KoromJ W Kupiec-Weglinski

Abstract

Chronic rejection remains the leading obstacle to long-term allograft survival. We have shown that treatment of sensitized rats with rapamycin (RPM) does not prevent progressive chronic-type cardiac allograft failure. Having documented the role of fibronectin (FN) in the allograft rejection cascade, we hypothesized that treatment with synthetic peptides that specifically block adhesive interactions between the connecting segment-1 (CS1)-binding domain of FN and alpha4beta1 integrin on circulating cells may prevent the development of chronic rejection in transplant recipients. Lewis rats were sensitized with Brown Norway skin grafts (day -7), followed by transplantation of LBNF1 hearts (day 0). Experimental animals were treated with RPM (day -7 to -1; 0.25 mg/kg/day i.p.), or RPM + CS1 peptides (day +7 to +13; 4 mg/kg/day i.v.), and euthanized at day 60. Unlike cardiac allografts in rats undergoing RPM monotherapy, those after adjunctive CS1 peptides had well preserved myocardial architecture and were free of arteriosclerotic lesions. Moreover, reverse transcription-polymerase chain reaction-based intragraft expression of transcripts for CD3, interferon-gamma, interleukin-12, monocyte chemoattractant protein-1, and transforming ...Continue Reading

References

Sep 1, 1991·Transplantation·N L TilneyD H Adams
Jun 1, 1991·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Y Shimizu, S Shaw
Feb 1, 1993·The Journal of Clinical Investigation·M P Bevilacqua, R M Nelson
Aug 1, 1994·The Journal of Clinical Investigation·S M WahlJ B McCarthy
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·K L HinesS M Wahl

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Citations

Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·W H RaoR D Camp
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Holly H BirdsallRoger D Rossen
Jan 24, 2008·Infection and Immunity·Manjusha M KulkarniBradford S McGwire
Jun 5, 2008·Cancer Immunology, Immunotherapy : CII·J E FildesN Yonan
Feb 22, 2002·Medicinal Research Reviews·Helena Yusuf-MakagiansarTeruna J Siahaan
Aug 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Holly H BirdsallRoger D Rossen
Jul 26, 2000·Transplantation·A J Coito, J W Kupiec-Weglinski
Sep 22, 2009·International Journal of Experimental Pathology·Ferdinan Almeida MeloWagner Luiz Tafuri
Mar 25, 2020·Immunity, Inflammation and Disease·Aurea V A da SilvaFernanda N Morgado
Jul 19, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Carla SensInaam A Nakchbandi
Mar 16, 2000·Cellular Immunology·D L BoyleG S Firestein
Oct 11, 2003·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Markus H C RichterHans Georg Olbrich

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