To investigate the involvement of
vitronectin, the
terminal complement complex (C5b-9), and the
vitronectin receptor in the pathogenesis of
membranous nephropathy, the immunohistochemical localization of these
antigens in the kidney was determined using the immunoperoxidase method and
monoclonal antibodies: antivitronectin, anti-SC5b-9 (neoantigen), and antivitronectin receptor (specific for alpha v beta 3 and alpha v). The subjects were 6 patients with
membranous nephropathy, and the controls were 2 patients with
minimal-change nephrotic syndrome. In
membranous nephropathy,
vitronectin was localized in subepithelial deposits and in epithelial cell foot processes and was intensely positive in the foot processes adjacent to subepithelial deposits.
C5b-9 showed a similar pattern of localization to
vitronectin. Both alpha v beta 3 and alpha v were localized in the basal portions of the foot processes of visceral epithelial cells as well as along the borders of these cells adjacent to the urinary space. Deposition at the former site was heavier than at the latter, and localization was especially prominent adjacent to the subepithelial deposits. In addition, alpha v was localized around and within some of the electron-lucent subepithelial deposits in the basement membrane. In contrast, the deposition of
vitronectin,
C5b-9, alpha v beta 3, and alpha v was always less intense in
minimal-change nephrotic syndrome than in
membranous nephropathy.
Vitronectin and
C5b-9 were localized to small parts of mesangium and glomerular basement membrane, while alpha v beta 3 and alpha v deposits showed no difference in intensity between the basal portions of the foot processes and the urinary border of the visceral epithelial cells. Thus,
membranous nephropathy featured increased localization of
vitronectin,
C5b-9, and
vitronectin receptors both within and around the subepithelial deposits, suggesting that the mechanism of
immune complex disposal via the
vitronectin receptor and the vitronectin-C5b-9 complex, associated with complement activation due to subepithelial
immune complex formation, may also be active.