Adhesion molecule interactions in human glomerulonephritis: Importance of the tubulointerstitium

Abstract

Infiltration of leukocytes into glomerular and interstitial regions of the kidney is a key event in the pathogenesis of human glomerulonephritis. This process is mediated by specific adhesion molecules, some of which are expressed in a coordinated fashion following endothelial cell activation. We have assessed the pattern of expression of the selectins (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 have correlated this with the degree of histological damage (tubular atrophy and interstitial fibrosis) and the intensity of the macrophage infiltrate. Sections were stained with the monoclonal antibodies using a standard 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, interstitium and in focal interstitial infiltrates and the presence of macrophages in these regions; (2) de novo tubular expression of ICAM-1 and VCAM-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 extraglomerular endothelium. These are also strongly correlated with the degree of chronic histological damage. There was, however, no correlation between glomerular expression of adhesion molecules or glomerular macrophage infiltration and chronic histological damage. Although expression of VCAM-1 by the glomerular mesangium was strongly correlated with the presence of cells staining for VLA-4 within the glomerulus, glomerular expression of adhesion molecules correlated poorly with their expression in other sites. These results show that coordinated up-regulation of adhesion molecule expression in the tubulointerstitium is associated with interstitial fibrosis and tubular atrophy and may contribute, therefore, to the progression of renal disease.

Increased expression of selectins in kidneys of patients with diabetic nephropathy

“…Interestingly, the grade of selectin expression in diabetic nephropathy was significantly higher than that in normal control subjects and in other glomerular diseases, including lupus nephritis and MPGN, in which infiltration of numerous macrophages was observed in the glomeruli (Table 4). A previous study reported that P-and E-selectin is expressed on extraglomerular vascular endothelium in human glomerulonephritis [32]. Pall et al [33] reported that E-selectin is expressed in the glomeruli of patients with diabetic nephropathy and severe pyelonephritis.…”

The N- and L-Type Calcium Channel Blocker Cilnidipine Suppresses Renal Injury in Dahl Rats Fed a High-Sucrose Diet, an Experimental Model of Metabolic Syndrome

“…These results are consistent with the pattern of ICAM-1 expression and ED-1-positive cell infiltration observed in this study. Recently, Roy-Chaudhury et al [42] suggested thatupregulation of adhesion molecule expression in the tubulointerstitium is associated with interstitial fibrosis and tubular atrophy, leading to the progression of renal disease. It has also been reported that in parallel with monocyte/macrophage infiltration, progressive interstitial accumulation of collagen I and IV, laminin and fibronectin occurs leading to tubulointerstitial damage [43].…”

Selective Regulation of ICAM-1 and RANTES Gene Expression after ICAM-1 Ligation on Human Renal Fibroblasts

“…After migration through the endothelium, however, the principal interaction of leukocytes is with cortical fibroblasts, which, under inflammatory conditions, have the phenotypic appearance of myofibroblasts (8,(12)(13)(14)(15)(16). This interaction is mediated through the increased expression of intercellular adhesion molecule-1 (ICAM-1) (17)(18)(19)(20)(21)(22) on the surface of the myofibroblasts and is central to the progression of inflammatory renal disease (2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

“…An influx of leukocytes, particularly macrophages and lymphocytes, into the glomerulus and subsequently into the cortical interstitium is characteristic of most forms of progressive renal disease [see reference 1 for review and references [2][3][4][5][6][7][8][9][10][11]. The initial interaction of the infiltrating cells is with the endothelial lining of the vessels.…”