Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium

P Roy-Chaudhury, B Wu, G King, M Campbell, A M Macleod, N E Haites, J G Simpson, D A Power

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Pages (from-to)127-34
Number of pages8
JournalKidney International
Volume49
Issue number1
Publication statusPublished - 1 Jan 1996

Fingerprint

Vascular Cell Adhesion Molecule-1
Integrin alpha4beta1
Glomerulonephritis
Intercellular Adhesion Molecule-1
L-Selectin
Lymphocyte Function-Associated Antigen-1
P-Selectin
E-Selectin
Macrophages
Staining and Labeling
Kidney
Atrophy
Alkaline Phosphatase
Fibrosis
Glomerular Mesangium
Endothelium
Disease Progression
Leukocytes
Up-Regulation
Endothelial Cells

Keywords

  • Biopsy
  • Cell Adhesion Molecules
  • Chronic Disease
  • Glomerulonephritis
  • Humans
  • Leukocytes
  • Selectins

Cite this

Roy-Chaudhury, P., Wu, B., King, G., Campbell, M., Macleod, A. M., Haites, N. E., ... Power, D. A. (1996). Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium. Kidney International, 49(1), 127-34.

Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium. / Roy-Chaudhury, P; Wu, B; King, G; Campbell, M; Macleod, A M; Haites, N E; Simpson, J G; Power, D A.

In: Kidney International, Vol. 49, No. 1, 01.01.1996, p. 127-34.

Research output: Contribution to journalArticle

Roy-Chaudhury, P, Wu, B, King, G, Campbell, M, Macleod, AM, Haites, NE, Simpson, JG & Power, DA 1996, 'Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium', Kidney International, vol. 49, no. 1, pp. 127-34.
Roy-Chaudhury P, Wu B, King G, Campbell M, Macleod AM, Haites NE et al. Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium. Kidney International. 1996 Jan 1;49(1):127-34.
Roy-Chaudhury, P ; Wu, B ; King, G ; Campbell, M ; Macleod, A M ; Haites, N E ; Simpson, J G ; Power, D A. / Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium. In: Kidney International. 1996 ; Vol. 49, No. 1. pp. 127-34.
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N2 - 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.

AB - 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.

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