Intercellular adhesion molecule-1 and tumour necrosis factor-alpha expression in human glomerulonephritis.

Abstract

The relationship between renal expression of intercellular adhesion molecule-1 (ICAM-1), glomerular hypercellularity, renal function and renal turnout necrosis factor-alpha (TNF-alpha) expression was examined by immunohistochemistry staining in 64 cases of human glomerulonephritis. Glomerular anti-ICAM-1 antibody staining was increased in most cases of IgA nephropathy and lupus nephritis, but was unchanged compared to normal in membranous nephropathy and minimal change disease, and reduced in glomerular sclerosis. However, when taken together, patients with mild or no glomerular hypercellularity (group A) showed normal ICAM-1 expression, those with moderate to severe hypercellularity (group B) had increased glomerular ICAM- 1 expression (P<0.001), while those with glomerular sclerosis (group C) had reduced glomerular ICAM-1 expression. Patients in groups B and C also showed a significant increase in tubular ICAM-1 expression (P<0.01) and interstitial infiltration of ICAM-1+ cells (P<0.001). Indeed, tubular ICAM-1 expression correlated with decreased creatinine clearance (r= -0.352; P<0.05). In situ hybridization demonstrated that increase in tubular ICAM-1 staining was due to de novo gene expression, rather than absorption of soluble ICAM-1 from the lumen. Focal expression of turnout necrosis factor-alpha was seen in areas of leucocyte infiltration and strong ICAM-1 expression. Indeed, TNF-alpha staining correlated with increased renal ICAM-1 expression in both glomerular and tubulointerstitial compartments (r = 0.81; P<0.01). To confirm that TNF-alpha can directly stimulate renal ICAM-1 expression, TNF-alpha was shown to transiently increase ICAM-1 mRNA synthesis for 4-8 h and cause a progressive increase in ICAM-1 protein on the surface of cultured human mesangial cells. In summary; (i) increased glomerular ICAM-1 expression was restricted to cases of moderate to severe hypercellularity; (ii) tubular ICAM-1 expression correlated with both creatinine clearance and interstitial infiltration of ICAM-1+ cells; and (iii) TNF-alpha expression was shown to correlate with the degree of renal ICAM-1 expression, suggesting that local TNF-alpha plays an important role in the up-regulation of ICAM-1 in human glomerulonephritis.