Intercellular adhesion molecule-1/leukocyte function associated antigen-1-mediated and complement receptor type 4-mediated infiltration and activation of glomerular immune cells in immunoglobulin A nephropathy.
Glomerular expression of intercellular adhesion molecule-1 (ICAM1) (CD54) and membrane cofactor protein (MCP; CD46) and positive infiltrating cells in leukocyte function associated antigen-1 (LFA1)alpha (CD11a) and C3bi receptors (CR3/CD11b, CR4/CD11c) were examined by the indirect immunoperoxidase method on 43 sets of repeated renal biopsy specimens from patients with immunoglobulin A nephropathy. Twenty-four-hour urine protein at the time of renal biopsy was also evaluated. Glomerular infiltration of LFA1alpha+ cells was significantly correlated with glomerular expression of ICAM1 (r = 0.494, P < 0.0001). Glomerular complement receptor type 4 (CR4)+ cells were significantly correlated with glomerular expression of MCP (r = 0.405, P < 0.0001). The glomerular expressions of ICAM1 and MCP were significantly correlated with each other (r = 0.700, P < 0.00001). The glomerular infiltrations of LFA1alpha+ and CR4+ cells were highly correlated with each other (r = 0.884, P < 0.00001), and both cell types were significantly correlated with urine protein (respectively, r = 0.426 and 0.478, P < 0.001 and 0.0001). When the change in these parameters between the time of the initial and follow-up biopsies was evaluated, there was a significant correlation between the change in glomerular expression of ICAM1 (DeltaICAM1) and MCP (DeltaMCP) as well as between the change in glomerular infiltration of LFA1alpha+ cells (DeltaLFA1alpha+) and CR4+ cells (DeltaCR4+). Both DeltaLFA1alpha+ and DeltaCR4+ were significantly correlated with the change in urine protein. These findings suggest that ICAM1/LFA1 interaction and MCP-mediated C3bi/C3biR interaction cooperate and participate in persistent glomerular infiltration of immune cells in immunoglobulin A nephropathy, and that these LFA1alpha+ and C3biR+ cells contribute to the induction of proteinuria.
Ootaka
T
T
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Saito
T
T
Soma
J
J
Yusa
A
A
Abe
K
K
D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D001706:Biopsy; D016022:Case-Control Studies; D003179:Complement C3b / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005922:Glomerulonephritis, IGA / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology; D011507:Proteinuria / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology*; D017463:Receptors, Complement 3b / Q000276:immunology; D013997:Time Factors
D015703:Antigens, CD; C497857:CD46 protein, human; D003181:Complement C4; D003169:Complement Inactivator Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D018799:Intercellular Adhesion Molecule-1; D003179:Complement C3b