Glomerulointerstitial interaction of adhesion molecules in IgA nephropathy and membranoproliferative glomerulonephritis.
The expression of two adhesion molecules, ICAM1 (CD54) and ICAM3 (CD50), infiltrating cells positive for their ligand, LFA1 (CD11a), and the markers of total leukocytes (CD45), T cells (CD3), granulocytes/monocytes (CD15), and macrophages (CD68) in renal interstitium were examined by an indirect immunoperoxidase method. The study was longitudinally performed on repeat renal biopsy specimens from 69 patients with two different proliferative glomerulonephritides: 43 with IgA nephropathy (IgAN) and 26 with membranoproliferative glomerulonephritis (MPGN). Interstitial ICAM1 (iICAM1) was mainly expressed on endothelium of peritubular venules and sometimes on tubular epithelium, and interstitial ICAM3 (iICAM3) on infiltrating immune cells. In IgAN, iICAM1 was significantly correlated with glomerular infiltration of LFA1+ cells (gLFA1) and CD68+ cells (gCD68) (r = 0.478/0.500; P < 0.0001) as well as CD3+ cells (gCD3) (r = 0.402; P < 0.002). In MPGN, iICAM1 was significantly correlated only with gCD68 (r = 0.382; P < 0.05). In both diseases, iICAM1 and iICAM3 were significantly correlated with interstitial infiltration of LFA1+ cells (iLFA1) and CD68+ cells (iCD68) (r = 0.616 to 0.815; P < 0.0001) and with interstitial infiltration of CD3+ cells (iCD3) (r = 0.474 to 0.816; P < 0.01). The iICAM3 was also significantly correlated with interstitial CD45+ cells (iCD45) (r = 0.672 in IgAN and 0.769 in MPGN; P < 0.00001). Interstitial infiltration of these immune cells was significantly correlated with the histologic parameters indicating renal injury, such as the index of glomerular lesion and the percent interstitial volume (r = 0.410 to 692; P < 0.05). Longitudinal analysis revealed that the parameters described above showed corresponding change with each other at the follow-up biopsy. These findings suggest that the glomeruler infiltration of T cells and macrophages influences the ICAM1/ICAM3 expression of the interstitial cells, especially In IgAN, and that ICAM1/LFA1 and ICAM3/LFA1 interactions contribute to the persistent infiltration of the interstitium by immune cells in both diseases.
Ootaka
T
T
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Saito
T
T
Soma
J
J
Sato
H
H
Abe
K
K
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002648:Child; D005260:Female; D005786:Gene Expression Regulation; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000473:pathology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1