Importance of the tubulointerstitium in human glomerulonephritis. II. Distribution of integrin chains β1, α1 to 6 and αV

Importance of the tubulointerstitium in human glomerulonephritis. II. Distribution of integrin chains β 1, α 1 to 6 and α V. Accumulation of extracellular matrix is important in the progression of glomerulonephritis. Since adherent cell types utilize integrins to bind and organize extracellular matrix proteins, we have assessed expression of the β 1 integrins in sequential sections from 85 human renal biopsies and 4 normal kidneys by immunohistochemical staining. Our results demonstrate strong correlations between expression of the α 5 chain within the interstitium, the α V chain on proximal and distal tubular epithelium and the presence of chronic histological damage. Moreover, staining for interstitial α 5 and proximal and distal tubular α V were also strongly associated with expression of certain adhesion molecules (ICAM-1, VCAM-1, E-selectin and L-selectin) and 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 study of adhesion molecules, there were also associations between expression of integrin chains within the glomerulus and tubulointerstitium. For example, there were strong positive associations between staining for α 5 on glomerular endothelium and its expression on extraglomerular vascular endothelium and between both mesangial α 1 and podocyte α 3 and tubular staining for the common β 1 subunit. While the functional significance of these associations is obscure, they suggest some kind of communication between cells in different sites in the kidney. There were also positive associations between staining for different integrins within the glomerulus, notably mesangial cell staining for α 2, glomerular endothelial cell staining for α 5 and glomerular epithelial cell α 3. These results suggest that there is a coordinated upregulation of integrin expression both within the tubulointerstitium and the glomerulus and that at least some of these integrins (interstitial α 5 and distal tubular α V) are associated with the expression of other adhesion molecules, macrophage infiltration and the presence of markers of disease progression (interstitial fibrosis and tubular atrophy).