ADHESION MOLECULES AND URINARY TUMOR-NECROSIS-FACTOR-ALPHA IN IDIOPATHIC MEMBRANOUS GLOMERULONEPHRITIS

Adhesion molecules are required in several physiological processes, bu t their altered function/expression is associated with the pathogenesi s of inflammatory diseases. In the present study on idiopathic membran ous glomerulonephritis (MGN) the expression of adhesion molecules (ICA M-1, VCAM-1, PECAM-1, E-selectin, LFA-1, Mac-1) was analyzed in differ ent cellular compartments of the kidney using an indirect immunoperoxi dase technique and monoclonal antibodies. Relationships between the ex pression of these molecules and the clinical and morphological activit y of the disease and the urinary excretion of tumor necrosis factor al pha (TNF-alpha) were studied in 20 patients. The results were compared with the findings in ten normal kidneys and urinary TNF-alpha in 17 h ealthy 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 glome rular endothelial cells (P < 0.01). Interstitial peritubular capillari es expressed significantly (P = 0.009) more E-selectin compared with t he controls. The interstitial compartment had a highly increased numbe r of cells expressing ICAM-1 in MGN (32.4 +/- 4.6 cells/high power fie ld) compared with the controls (9.4 +/- 1.2; P < 0.001). Also, cells e xpressing VCAM-1 (10.2 +/- 1.6 vs. 2.8 +/- 1.9; P = 0.005), PECAM-1 (2 5.9 +/- 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 peritubu lar capillaries (I = 0.63, P = 0.004). The number of LFA-1 expressing inflammatory cells in the interstitium correlated with peritubular cap illary E-selectin (r = 0.8, P < 0.001) and interstitial ICAM-1 (r = 0. 61, P = 0.009) expression, but histological alterations did not correl ate with the expression of adhesion molecules. Tumor necrosis factor-o r excretion was significantly increased in MGN (41 +/- 8 pg/mg creatin ine) compared with the controls (13 +/- 2; P = 0.001), and in particul ar, 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 pro teinuria but also to increased urinary TNF-alpha excretion. These map serve as triggers for the up-regulation of adhesion molecules in the p eritubular capillaries and interstitial cells thus enhancing the devel opment of the interstitial injury.