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 transplantation.
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.
Grooby
W L
WL
Transplantation Immunology Laboratory, The Queen Elizabeth Hospital, Woodville, South Australia.
Krishnan
R
R
Johnston
J K
JK
Rao
M M
MM
Russ
G R
GR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004338:Drug Combinations; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D011184:Postoperative Period; D012756:Sheep; D013997:Time Factors; D014018:Tissue Distribution; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1