COMBINED ANTI-VASCULAR CELL ADHESION MOLECULE-1 AND ANTI-LEUKOCYTE FUNCTION-ASSOCIATED MOLECULE-1 MONOCLONAL ANTIBODY THERAPY DOES NOT PROLONG ALLOGRAFT SURVIVAL IN AN OVINE MODEL OF RENAL TRANSPLANTATION1

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Abstract

This study investigates the therapeutic efficacy of an anti-vascular cell adhesion molecule (VCAM)-1 monoclonal antibody (mAb), alone or in combination with an anti-leukocyte function-associated-1 mAb, in prolonging allograft survival in an ovine model of renal transplantation. The kinetics of VCAM-1 induction and expression during renal allograft rejection have also been studied.

Sheep receiving anti-ovine VCAM-1 antibody demonstrated graft failure at a mean of 8.4 (± SD; 0.7) days after transplantation compared with 9.3 (± 0.5) days after transplantation for the group given control antibody and 7.7 (± 0.3) days after transplantation in the animals given the combined anti-VCAM-1 and anti-leukocyte function-associated-1 mAb therapy. VCAM-1 expression was detected in the allografts at day 1 after transplantation, with peak expression detected by day 5. Tubular expression of VCAM-1 was minimal, with sparse focal staining at the basolateral surfaces. The degree of mononuclear cell infiltrate in the allografts paralleled the progressive increase in VCAM-1 expression after transplantation, and there was no difference in the level of mononuclear cell infiltrate compared with controls.

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