ICAM-1 and VCAM-1 expression in accelerated cardiac allograft arteriopathy and myocardial rejection are influenced differently by cyclosporine A and tumour necrosis factor-alpha blockade.
Expression of the vascular cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) occurs in allograft myocardium and in coronary arteries, promoting adhesion and transendothelial migration of inflammatory cells. We therefore investigated, in cholesterol-fed rabbits 9-10 days following heterotopic cardiac transplantation, whether the reduction of both myocardial rejection and graft arteriopathy with cyclosporine A (CsA) or graft arteriopathy alone with tumour necrosis factor-alpha soluble receptor (TNFsr) was associated with suppression of ICAM-1 and VCAM-1 expression. Host hearts showed negative immunostaining for these adhesion molecules, whereas donor specimens from untreated (control) rabbits showed moderate immunostaining for ICAM-1 and weaker immunostaining for VCAM-1 in the coronary arteries, myocardium (cardiac myocytes), and perivenular regions. The selective reduction of the coronary arteriopathy with TNFsr was associated with somewhat reduced expression of these adhesion molecules in the arteries, whereas CsA also suppressed myocardial rejection and markedly decreased both vascular and myocyte expression of ICAM-1 and VCAM-1.
Molossi
S
S
Division of Cardiovascular Research, Hospital for Sick Children, Toronto, Canada.
Clausell
N
N
Sett
S
S
Rabinovitch
M
M
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003331:Coronary Vessels / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D018124:Receptors, Tumor Necrosis Factor; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D018124:Receptors, Tumor Necrosis Factor; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016572:Cyclosporine