Munksgaard International Publishers ISSN 1600-6135 Acute Cellular Rejection Following Human Heart Transplantation is Associated with Increased Expression of Vitronectin Receptor (Integrin avb3)

The vitronectin receptor (integrin avb3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atheroscler-osis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of avb3. We also determined whether fibronectin receptor (a5b1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyo-cardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n 10; grade 1A, n10; grade 2, n10; grade 3A, n10). Biopsies were obtained 2–4weeks after cardiac trans-plantation. Immunoperoxidase staining was performed for avb3, tissue factor, and a5b1, and protein levels were further determined by Western blot analysis. Speci-mens with grade 2 and grade 3A rejection showed posi-tive staining of avb3 in lymphocytic aggregates and vas-cular endothelial cells. By immunoblotting, we iden-tified significantly increased expression of avb3 in the presence of acute rejection, grade 2 (3-fold, p 0.01) and grade 3A (3.6-fold, p 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of a5b1 or tissue factor. Acute cellular rejec-tion, a process characterized by T-lymphocyte acti-vation and release of inflammatory cytokines, is associ-ated with increased expression of avb3