The beta1-integrin family of adhesion molecules is supposed to mediate cell-to-matrix interactions involved in a variety of immune reactions, especially in those associated with tissue remodelling. In an attempt to determine the role of beta1-integrins in the initiation and maintenance of fibrotic deposition observed in chronic rejection after liver transplantation, we immunohistochemically analysed the expression of different extracellular matrix components and the very late antigen (VLA) family of beta1-integrins in 11 samples of chronically rejected human liver allografts and compared results to findings in acutely rejected transplants and nontransplanted chronic inflammatory livers. In contrast to normal liver specimens, chronically rejected human liver allografts displayed a general overexpression of matrix components along sinusoids throughout the tissue and an additional characteristic accumulation in pericentral areas. Accordingly, VLA-1, -5 and -6 demonstrated a linear upregulation or de novo expression on sinusoidal lining cells, VLA-1 and VLA-4 additionally displayed concentration within pericentral fibrotic deposits. VLA-2 and -3 were only sporadically found. In accordance with findings in chronic rejection, chronic inflammatory livers showed overexpression of VLA-1, -5 and -6 within sinusoids and accumulation of VLA-1 and -4 in fibrotic septa. In contrast, acutely rejected allografts displayed slight overexpression of ECM components without characteristic accumulates, hence beta1-integrins were seen to be equally distributed throughout the parenchyma. Altogether, our analysis showed an upregulation of integrin receptors which corresponded to the extent of ECM deposition and thus suggested an important role for these molecules in the iniation of fibrosis observed in these specimens. Individual integrins showed different expression patterns within sinusoids and fibrotic areas, indicating distinct roles in differential stages of matrix accumulation, but induction patterns were generally similar in chronic inflammatory and chronically rejected livers, suggesting independence of the underlying disease.
