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Leukocyte infiltration and intercellular adhesion molecule-1-mediated cell interactions in immunoglobulin A
P Arrizabalaga1, M Solé, L Quintó
1Service of Nephrology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Background:
Mononuclear leukocytes have a role in immunoglobulin (Ig) A nephropathy. Renal leukocyte recruitment is mediated by adhesive interactions between leukocytes and their ligands on renal cells.
Methods:
We assessed interstitial and glomerular leukocytes using an avidin-biotin-peroxidase method with monoclonal antibodies (MAbs) against leukocytes (CD45), beta2-integrin (CD18), macrophages (CD14), T cells (CD3) and T-cell subsets (CD4, CD8), intercellular adhesion molecule-1 (ICAM-1) (CD54), and HLA class II antigens. We analyzed their relation with the abnormal expression of ICAM-1 on proximal tubular epithelium in sequential renal sections from 57 patients with IgA nephropathy stratified by degrees of interstitial cellular infiltration as seen by light microscopy.
Results:
In IgA nephropathy without infiltration (n = 15) and with interstitial cellular infiltration of 1+ by light microscopy (n = 11), ICAM-1 expression on vascular endothelium was unchanged with respect to that observed in the normal kidney; the proximal tubular epithelium was negative for this stain. Moreover, in IgA nephropathy with interstitial cellular infiltration greater than or equal to 2+ by light microscopy (n = 31), ICAM-1+ stain was seen on proximal tubular epithelium. The value of ICAM-1+ tubule staining was significantly (P = .0004) higher in the biopsies with a higher degree of interstitial cellular infiltration seen by light microscopy. The tubular ICAM-1+ stain was significantly associated with the number of interstitial leukocytes identified by the MAbs tested and correlated (P < .05) with CD45+ (r = 0.59), CD14+ (r = 0.54), and CD3+ (r = 0.51) interstitial leukocytes in IgA nephropathy with interstitial cellular infiltration by light microscopy. Interstitial ICAM-1+ cells and interstitial CD18+ leukocytes were correlated (r = 0.85, P < .001). Correlation was found between the value of ICAM-1+ tubule staining and the number of CD45+ (r = 0.87, P < .01), CD14+ (0.58, P < .05), and CD8+ (r = 0.68, P < .05) glomerular leukocytes.
Conclusions:
Our results suggest that tubular and interstitial ICAM-1+ cells may participate in adhesive interactions with interstitial leukocytes. Epithelial tubular cells expressing ICAM-1 may be a marker of tubulointerstitial disturbance upregulated by interstitial and glomerular infiltration of macrophages and T cells in IgA nephropathy.