THE ASSOCIATION OF THE INDUCTION OF VASCULAR CELL-ADHESION MOLECULE-1 WITH CYTOMEGALOVIRUS ANTIGENEMIA IN HUMAN HEART ALLOGRAFTS

Previous studies have suggested that during acute heart allograft rejection the expression of vascular adhesion molecules is induced. This study was designated to investigate the expression of three adhesion molecules ICAM-1 (CD 54), VCAM-1, and ELAM-1, and the counter-ligands LFA-1 (CD 18), Mac-1 (CD 11b/CD 18), and VLA-4 (CD 49d) in frozen sections of endomyocardial biopsies (EMB) of heart allografts in relation to onset of CMV infection recorded as CMV antigenemia. The expression of MHC class II antigens and interleukin-2-receptor was also analyzed. A total of 105 EMBs and 840 immunoperoxidase stainings obtained from 21 heart transplant recipients were analyzed. EMBs from 9 patients with CMV infections, 5 patients with rejections, and 7 patients with a noncomplicated postoperative course were included. An induction of VCAM-1 occurred in relation to onset of CMV antigenemia. The expression of VCAM-1 remained elevated for several weeks declining slowly to control levels. Associated with CMV infection, capillary expression of VCAM-1 (P<0.001) and ELAM-1 (P<0.03) was significantly induced when compared with control biopsies. ICAM-1 expression was always seen in capillaries-and also in controls. A striking difference in the expression of VCAM-1 during rejection and CMV infection was observed: in most rejecting biopsies only a few capillaries stained faintly for VCAM-1, whereas during CMV infection multifocal intense staining was found (P< 0.0001). Induction of ELAM-1 was associated with acute rejections. In general, the expression of ligand counterparts was at a higher level during rejection compared with CMV infection. However, a short-term induction of VLA-4 occurred after the onset of CMV antigenemia (N.S.). Thus, the VCAM-1/VLA-4 ligand pair may play an important role in adhesion of lymphocytes and monocytes to capillary endothelium during active CMV infection and may also contribute to the pathogenesis of increased vasculopathic changes reported in CMV-infected heart transplant recipients.