IMPORTANCE OF THE TUBULOINTERSTITIUM IN HUMAN GLOMERULONEPHRITIS .2. DISTRIBUTION OF INTEGRIN CHAINS BETA-1, ALPHA-1 TO ALPHA-6 AND ALPHA-V

Accumulation of extracellular matrix is important in the progression o f glomerulonephritis. Since adherent cell types utilize integrins to b ind and organize extracellular matrix proteins, we have assessed expre ssion of the beta 1 integrins in sequential sections from 85 human ren al biopsies and 4 normal kidneys by immunohistochemical staining. Our results demonstrate strong correlations between expression of the alph a 5 chain within the interstitium, the alpha V chain on proximal and d istal tubular epithelium and the presence of chronic histological dama ge. Moreover, staining for interstitial alpha 5 and proximal and dista l tubular alpha V were also strongly associated with expression of cer tain adhesion molecules (ICAM-1, VCAM-1, E-selectin and L-selectin) an d the presence of macrophages within the interstitium, which have been linked, in an earlier study, with the degree of chronic histological damage and disease progression. However, in contrast to our earlier st udy of adhesion molecules, there were also associations between expres sion of integrin chains within the glomerulus and tubulointerstitium. For example, there were strong positive associations between staining for alpha 5 on glomerular endothelium and its expression on extraglome rular vascular endothelium and between both mesangial alpha 1 and podo cyte alpha 3 and tubular staining far the common beta 1 subunit. While the functional significance of these associations is obscure, they su ggest some kind of communication between cells in different sites in t he kidney. There were also positive associations between staining for different integrins within the glomerulus, notably mesangial cell stai ning for alpha 2, glomerular endothelial cell staining for alpha 5 and glomerular epithelial cell alpha 3. These results suggest that there is a coordinated upregulation of integrin expression both within the t ubulointerstitium and the glomerulus and that at least some of these i ntegrins (interstitial alpha 5 and distal tubular alpha V) are associa ted with the expression of other adhesion molecules, macrophage infilt ration and the presence of markers of disease progression (interstitia l fibrosis and tubular atrophy).