Signs of endothelial inflammation in human heart allografts.
The expression of leucocyte adhesion facilitating molecules on endothelia is a major stimulus for tissue inflammation and cell infiltration. Recently, specific receptor ligands have been identified that mediate cellular adhesion of lymphocytes or monocytes. In the present study, sequential changes in the expression of immune adhesion receptors (LFA-1, CD2) and their ligand molecules (ICAM-1, LFA-3) were studied in heart allografts during rejection. Consecutive endomyocardial biopsies (n = 157; d.3-1013) of 16 heart transplanted patients were studied using monoclonal antibodies and standard immunohistology. In biopsies that showed no rejection, immune adhesion molecules (ICAM-1) were weakly expressed on a few endothelial cells. ICAM-1 was induced on blood vessel and capillary endothelia during rejection. After treatment, expression declined, as did the clearance of infiltrates. Occasionally, ICAM-1 persisted on capillaries compared with class II MHC expression. Weak LFA-3 induction on endothelia was observed in acute rejection, similar to ICAM-1, however LFA-3 expression was more restricted. Infiltrating lymphocytes expressed the adhesion receptor molecules LFA-1 and/or CD2. The variability of expression of ICAM-1 and FA-3 ligand molecules was related to the inflammatory changes in the graft during acute rejection. It is likely that the induction of adhesion ligand molecules in tissue is regulated by systemic and local release of cytokines, and is an initiating step in graft infiltration. The demonstration of immune adhesion-molecule induction in heart graft rejection may also be applicable to inflammatory heart disease in viral myocarditis.
Department of Surgery, Medical School, Hannover, Germany.
G
G
Steinhoff
M
M
Behrend
A
A
Haverich
D015703:Antigens, CD / Q000276:immunology; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1