ADHESION MOLECULE INTERACTIONS IN HUMAN GLOMERULONEPHRITIS - IMPORTANCE OF THE TUBULOINTERSTITIUM

Infiltration of leukocytes into glomerular and interstitial regions of the kidney is a key event in the pathogenesis of human glomerulonephr itis. This process is mediated by specific adhesion molecules, some of which are expressed in a coordinated fashion following endothelial ce ll activation. We have assessed the pattern of expression of the selec tins (E, P and L), and the counter-receptors LFA-1 and ICAM-1, and VLA -4 and VCAM-1 in 119 renal biopsies using sequential sections, and hav e correlated this with the degree of histological damage (tubular atro phy and interstitial fibrosis) and the intensity of the macrophage inf iltrate. Sections were stained with monoclonal antibodies using a stan dard alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. There were strong correlations between the following: (1) expression of LFA-1, VLA-4, and L-selectin in the periglomerular region, intersti tium and in focal interstitial infiltrates and the presence of macroph ages in these regions; (2) de novo tubular expression of ICAM-1 and VC AM-1; (3) staining for ICAM-1 and VCAM-1 on focal cellular infiltrates within the interstitium; and (4) staining for E- and P- selectin on e xtraglomerular endothelium. These also strongly correlated with the de gree of chronic histological damage. There was, however, no correlatio n between glomerular expression of adhesion molecules or glomerular ma crophage infiltration and chronic histological damage. Although expres sion of VCAM-1 by the glomerular mesangium was strongly correlated wit h the presence of cells staining for VLA-4 within the glomerulus, glom erular expression of adhesion molecules correlated poorly with their e xpression in other sites. These results show that coordinated up-regul ation of adhesion molecule expression in the tubulointerstitium is ass ociated with interstitial fibrosis and tubular atrophy and may contrib ute, therefore, to the progression of renal disease.