Adhesion molecules and urinary tumor necrosis factor-alpha in idiopathic membranous glomerulonephritis

Abstract

Adhesion molecules are required in several physiological processes, but their altered function/expression is associated with the pathogenesis of inflammatory diseases. In the present study on idiopathic membranous glomerulonephritis (MGN) the expression of adhesion molecules (ICAM-1, VCAM-1, PECAM-1, E-selectin, LFA-1, Mac-1) was analyzed in different cellular compartments of the kidney using an indirect immunoperoxidase technique and monoclonal antibodies. Relationships between the expression of these molecules and the clinical and morphological activity of the disease and the urinary excretion of tumor necrosis factor alpha (TNF-alpha) were studied in 20 patients. The results were compared with the findings in ten normal kidneys and urinary TNF-alpha in 17 healthy subjects. The expression of adhesion molecules in glomeruli and tubules was unchanged apart from a diminished expression of VCAM-1 (P = 0.014) in glomerular parietal epithelial cells and PECAM-1 in glomerular endothelial cells (P < 0.01). Interstitial peritubular capillaries expressed significantly (P = 0.009) more E-selectin compared with the controls. The interstitial compartment had a highly increased number of cells expressing ICAM-1 in MGN (32.4 +/- 4.6 cells/high power field) compared with the controls (9.4 +/- 1.2; P < 0.001). Also, cells expressing VCAM-1 (10.2 +/- 1.6 vs. 2.8 +/- 1.9; P = 0.005). PECAM-1 (25.9 +/- 5.3 vs. 7.4 +/- 2.1; P = 0.006), and LFA-1 (20.4 +/- 3.6 vs. 8.3 +/- 1.5; P = 0.041) were increased in the interstitium. Proteinuria correlated particularly with the expression of E-selectin in peritubular capillaries (r = 0.63, P = 0.004). The number of LFA-1 expressing inflammatory cells in the interstitium correlated with peritubular capillary E-selectin (r = 0.8, P < 0.001) and interstitial ICAM-1 (r = 0.61, P = 0.009) expression, but histological alterations did not correlate with the expression of adhesion molecules. Tumor necrosis factor-alpha excretion was significantly increased in MGN (41 +/- 8 pg/mg creatinine) compared with the controls (13 +/- 2; P = 0.001), and in particular, it correlated with the interstitial expression of LFA-1 (r = 0.71, P = 0.002). This study suggests that active MGN leads not only to proteinuria but also to increased urinary TNF-alpha excretion. These may serve as triggers for the up-regulation of adhesion molecules in the peritubular capillaries and interstitial cells thus enhancing the development of the interstitial injury.