THROMBOSPONDIN IN HUMAN GLOMERULOPATHIES - A MARKER OF INFLAMMATION AND EARLY FIBROSIS

Extensive damage is thought to occur to endothelial cells in renal vas culitis and other glomerulopathies. The state of inflammation of these endothelial cells was investigated through the use of a panel of mono clonal antibodies (MAb) directed against thrombospondin (TSP), von Wil lebrand 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 glom erlonephritis (GN), and diabetic GN but does not in normal kidney. In contrast, very limited areas are stained by, LYP10 in minimal change n ephropathy and Berger's disease On paraffin-embedded specimens these a reas stained by LYP10 appear edematous and early fibrous. Up-regulatio n of vWF and ICAM-1 is matched by an increased binding of LYP10 to the interstitium In addition, fibrous cresents in injured glomeruli are s tained by LYP10. This study, reports for the first time an increased T SP secretion in glomerulopathies. Such TSP secretion may be part of ph ysiological adaptive changes associated with inflammation and early fi brosis.