Thrombospondin in human glomerulopathies. A marker of inflammation and early fibrosis.
Extensive damage is thought to occur to endothelial cells in renal vasculitis and other glomerulopathies. The state of inflammation of these endothelial cells was investigated through the use of a panel of monoclonal antibodies (MAb) directed against thrombospondin (TSP), von Willebrand factor (vWF), integrins (alpha IIb beta 3, alpha v beta 3), CD36, and classical markers of inflammation (P-selectin, E-selectin, ICAM-1, VCAM). Results show that the anti-TSP MAb (LYP10) stains large areas of interstitium in focal sclerosis, vasculitis, membranous glomerulonephritis (GN), and diabetic GN but does not in normal kidney. In contrast, very limited areas are stained by LYP10 in minimal change nephropathy and Berger's disease. On paraffin-embedded specimens these areas stained by LYP10 appear edematous and early fibrous. Up-regulation of vWF and ICAM-1 is matched by an increased binding of LYP10 to the interstitium. In addition, fibrous crescents in injured glomeruli are stained by LYP10. This study reports for the first time an increased TSP secretion in glomerulopathies. Such TSP secretion may be part of physiological adaptive changes associated with inflammation and early fibrosis.
McGregor
B
B
Hopital Edouard Herriot, Lyon, France.
Colon
S
S
Mutin
M
M
Chignier
E
E
Zech
P
P
McGregor
J
J
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology; D004317:Doxorubicin / Q000032:analysis / Q000276:immunology; D019040:E-Selectin; D004727:Endothelium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D005921:Glomerulonephritis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000032:analysis / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D007668:Kidney / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000378:metabolism; D019699:Thrombospondins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016023:Integrins; D008562:Membrane Glycoproteins; D019699:Thrombospondins; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D004317:Doxorubicin