Inhibition of accelerated coronary atherosclerosis with short-term blockade of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in a heterotopic murine model of heart transplantation.
BACKGROUND
Graft arteriopathy limits the long-term survival of allograft recipients. Cardiac allografts in mice develop graft coronary arteriopathy similar to that observed in clinical chronic rejection in human beings. We found that antiintercellular adhesion molecule-1 (ICAM-1) and antilymphocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (mAbs) induce immunologic tolerance to mice with cardiac allografts.


METHODS
To evaluate the effects of short-term administration of anti-ICAM-1 plus anti-LFA-1 mAbs in preventing graft arteriopathy, we treated C3H/He mice that received cardiac allografts from BALB/c mice with anti-ICAM-1 plus anti-LFA-1 mAbs for the first 5 days after transplantation. For control studies, FK506 was administered daily to other allograft recipients. Allografts were harvested on day 60. Immunohistochemical analysis was used to detect the expression of ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and in situ reverse transcriptase polymerase chain reaction was performed to detect platelet-derived growth factor (PDGF)-B mRNA expression in the graft arteries.


RESULTS
Allografts from mice that received FK506 treatment daily showed significant neointimal thickening with increased expression of ICAM-1, VCAM-1, and PDGF-B mRNA, whereas there was almost no intimal thickening and ICAM-1, VCAM-1, and PDGF-B mRNA expression in the mice that received anti-ICAM-1 plus anti-LFA-1 mAbs.


CONCLUSIONS
Short-term blockade of ICAM-1 and LFA-1 adhesion not only induces immunologic tolerance to cardiac allografts but also prevents graft arteriopathy.
Suzuki
J
J
First Department of Internal Medicine, School of Medicine, Shinshu University, Nagano, Japan.
Isobe
M
M
Yamazaki
S
S
Horie
S
S
Okubo
Y
Y
Sekiguchi
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003324:Coronary Artery Disease / Q000517:prevention & control*; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000502:physiology; D011183:Postoperative Complications / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis; D016559:Tacrolimus / Q000494:pharmacology; D016042:Transplantation, Heterotopic
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D016559:Tacrolimus