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J Reconstr Microsurg 2001; 17(7): 511-518
DOI: 10.1055/s-2001-17753
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Combination of Anti-ICAM-1 and Anti-LFA-1 Monoclonal Antibody Therapy Prolongs Allograft Survival in Rat Hind-Limb Transplants

Kagan Ozer, Maria Siemionow
  • Department of Plastic and Reconstructive Surgery, The Cleveland Clinic Foundation, Cleveland, OH
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Publication History

Publication Date:
12 October 2001 (online)

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ABSTRACT

Immunosuppressive effects of monoclonal antibodies against adhesion molecules were validated in solid organ transplants. There have been only a few reports on the effect of these antibodies on limb transplantation. In this study, the authors investigated the effects of anti-ICAM-1 and anti-LFA-1 therapy in the rat hind-limb-cremaster transplantation model. Twenty transplantations were performed across a major histocompatibility barrier between Lewis Brown Norway (LBN, RT-1l+n) and Lewis (LEW, RT-1l) rats in four experimental groups of five animals each. Group 1 animals received only vehicle solution; Groups 2 and 3 received monoclonal antibodies against ICAM-1 and LFA-1, respectively; Group 4 received a combination dose. Treatments were continued for 7 days. Clinical signs of rejection were noted daily, and correlated with in vivo microcirculatory measurements.

The activation of adhering leukocytes was significantly lower in rats treated with anti-ICAM-1, anti-LFA-1, and combination than in controls (p < 0.05). Transmigrating leukocytes were also reduced in antibody-treated groups, when compared to the control group (p < 0.05). The mean number of rolling lymphocytes was significantly reduced only in the combination group (p < 0.05). Endothelial edema index, a measure of endothelial swelling, was lowest in the combination group (p < 0.05). The first clinical signs of rejection were noted between the 5th and 9th days in the control group, on the 9th day in the anti-ICAM-1 or anti-LFA-1 groups, and on the 13th day with combination therapy.

Monoclonal antibodies against LFA-1 or ICAM-1 alone inhibit the activation of leukocytes at the microcirculatory level but do not prolong graft survival. However, the combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies significantly prolonged allograft survival in this composite tissue transplantation model.

KEYWORD

Transplant rejection - limb transplantation - rat hind-limb-cremaster transplantation model - ICAM-1 MAb - LFA-1 MAb

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