Renal allograft rejection: expression and function of VCAM-1 on tubular epithelial cells

Abstract

SUMMARY: The interaction between vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) is known to play an important role in stabilizing the adhesion of lymphocytes to endothelial cells. Such cellular adhesion is crucial to many immunological processes including lymphocyte-mediated cell lysis. In this study the expression of VCAM-I on renal tubular epithelial cells is demonstrated on biopsy sections recovered during acute renal allograft rejection. Experiments performed using epithelial cells cultured from renal tubules show that VCAM-1 is up-regulated by addition of the inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Combination of TNF-α and IFN-γ synergized to induce high levels of VCAM-1 expression. Further experiments demonstrated that the cytokines produced by activated lymphocytes in mixed leucocyte culture also up-regulate expression of VCAM-1. Assays of the adhesion of lymphoid cells to cultured renal epithelial cells showed that cytokine pretreatment of the renal cells enhanced the binding of lymphoid cells. The proportion of bound lymphoid cells was significantly reduced by addition of an antibody capable of blocking the interaction of VCAM-1 with VLA-4. This result indicated that the VCAM-1 induced on renal epithelial cells by inflammatory cytokines is functionally capable of binding VLA-4, thereby enhancing the adhesion of potentially graft-damaging lymphoid cells.