Effect of anti-intercellular adhesion molecule-1 and anti-leukocyte function associated antigen-1 monoclonal antibodies on rat-to-mouse cardiac xenograft rejection

Surgery
S MiwaS Kawasaki

Abstract

The interaction between intercellular adhesion molecule-1 (ICAM-1) and its ligand, leukocyte function associated antigen-1 (LFA-1), is especially relevant in allograft rejection. We have previously shown that the simultaneous blockade of ICAM-1 and LFA-1 by monoclonal antibodies (mAbs) results in specific immunologic tolerance to cardiac allograft in a mouse model. We evaluated the roles of these adhesion molecules in xenograft rejection by using a rat-to-mouse concordant xenograft model to identify critical molecules for immunosuppression. Lewis rat hearts transplanted into C3H/He mice were rejected within 5 to 7 days without treatment. A significant prolongation of xenograft survival (mean survival time, 11.6 days) was observed after treatment with anti-rat ICAM-1 and anti-mouse LFA-1 mAbs, when compared with nontreated mice or mice treated with different combinations of mAbs. Graft survival was prolonged in mice treated with FK506 (1 mg/kg/day), anti-rat ICAM-1, and anti-mouse LFA-1 mAbs (mean survival time, 22.2 days), whereas the same dose of FK506 alone was not effective. The mixed lymphocyte reaction showed that a combination of mAbs against mouse LFA-1-rat ICAM-1 and rat LFA-1-mouse ICAM-1 significantly inhibited the pr...Continue Reading

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Citations

Sep 29, 2011·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·W H KitchensM L Ford
Jan 26, 2006·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M R Nicolls, R G Gill
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