Expression of the Molecule Detectable by Anti-Propolypeptide of von Willebrand Factor Antibody in Rat Mesangial Cells in Anti-Thy 1.1 mAb 1-22-3 Induced Glomerulonephritis: A Marker of Injured Mesangial Cells

Abstract

We have previously reported that propolypeptide of von Willebrand factor (pp-vWF) binds to collagen with an affinity comparable to that of mature vWF, inhibits collagen-induced platelet aggregation, is cross-linked with laminin, and also serves as a ligand for very-late antigen 4 integrin. These observations from in vitro experiments suggest that pp-vWF is incorporated in the extracellular matrix and affects the cell-matrix interaction and that pp-vWF functions in leukocyte recruitment to inflammatory and vascular injury sites. We, therefore, hypothesize that pp-vWF might be involved in the induction and/or progression of mesangial proliferative glomerulonephritis. To test this hypothesis, we examined the kinetics of the immunostaining of the molecule detectable by an affinity-purified anti-pp-vWF antibody in rat glomeruli in monoclonal antibody 1-22-3 induced glomerulonephritis. Immunostaining by pp-vWF antibody was observed in the nuclear rim of mesangial cells in monoclonal antibody 1-22-3 induced glomerulonephritis. Positive staining first appeared on day 10 after monoclonal antibody injection, when mesangial cell proliferation and mesangial matrix expansion had already begun. Staining was still detected on day 56, when morphologic alterations observed by light microscopy had been normalized. The pp-vWF antibody recognized molecule appeared later than α-smooth muscle actin or collagen type I. Positive staining was not detected in cultured mesangial cells. It should be noted that the positive staining by pp-vWF antibody in mesangial cells was still detected in previously injured glomeruli that have almost recovered normal morphology. These observations indicate that positive staining by pp-vWF antibody could be a very useful marker for identifying a past episode of injury in mesangial cells.