Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection

Abstract

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are important in endothelial cellleukocyte interactions. In this sequential study, the expression of ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 as well as major histocompatibility complex class I1 antigens (MHC class II), and interleukin-2-receptor (IL-2R) were investigated during the development of chronic renal allograft rejection in a rat model. The time-related expression of adhesion molecules and their ligands in the graft was correlated to the chronic allograft damage index (CADI). In association with an initial short immune activation, there was a significant ICAM-1 and VCAM-1 induction in the vascular endothelium and the tubular epithelium. In the interstitium, there was infiltration of lymphocytes expressing ligand molecules VLA-4 and LFA-l, as well as activation markers MHC class I1and IL-2R. Thereafter, the expression declined together with the increase of CADI-values. In end-stage chronic rejection, there was practically no expression of ICAM-1 and VCAM-1. In the interstitium, there were only few ligand-expressing leukocytes. In conclusion, adhesion molecules and their ligands are involved in the induction phase of the process but no longer in the later stages of chronic rejection.

Selective Regulation of ICAM-1 and RANTES Gene Expression after ICAM-1 Ligation on Human Renal Fibroblasts

“…After migration through the endothelium, however, the principal interaction of leukocytes is with cortical fibroblasts, which, under inflammatory conditions, have the phenotypic appearance of myofibroblasts (8,(12)(13)(14)(15)(16). This interaction is mediated through the increased expression of intercellular adhesion molecule-1 (ICAM-1) (17)(18)(19)(20)(21)(22) on the surface of the myofibroblasts and is central to the progression of inflammatory renal disease (2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

“…An influx of leukocytes, particularly macrophages and lymphocytes, into the glomerulus and subsequently into the cortical interstitium is characteristic of most forms of progressive renal disease [see reference 1 for review and references [2][3][4][5][6][7][8][9][10][11]. The initial interaction of the infiltrating cells is with the endothelial lining of the vessels.…”

Adhesive functions of both chains of VLA‐integrins are not fully conserved across the human–porcine species barrier: implications for xenotransplantation

“…In addition, VLA‐integrins are important in rejection, and it has been demonstrated that blockade of integrin‐to‐ligand interactions significantly alleviates inflammatory processes, increases organ survival times and may even induce states of indefinite organ acceptance or tolerance [35–43]. As both chains take part in adhesive as well as signaling processes, the conserved or non‐functional crossreactivity of the individual chains may allow for species‐specific blockade of key steps in the xenogeneic rejection cascade.…”

Reduction of ICAM-1 and LFA-1-positive leukocytes in the perivascular space of arteries under mycophenolate mofetil therapy reduces rat heart transplant vasculopathy

“…Monoclonal antibodies to ICAM-1 and CD11a (LFA-1) (Pharmingen, San Diego, CA) were used for immunohistochemical analyses as previously described. 29 Specimens were pre-incubated with primary antibodies for 80 minutes at room temperature. Monoclonal antibody staining was detected using the alkaline phosphatase (APAAP) technique.…”