['Our previous work in the acute puromycin aminonucleoside nephrosis (PAN) model has demonstrated up-regulation of heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA and protein within glomerular epithelial cells (GECs) prior to the onset of proteinuria.', 'To determine whether increased HB-EGF expression in the acute PAN model contributes to the pathogenesis of proteinuria, a monoclonal antibody (DE10) was produced against recombinant human HB-EGF.', 'The specificity of DE10 for human HB-EGF was confirmed by enzyme-linked immunosorbent assay, immunohistochemical staining, and flow cytometry of transfected cells expressing human and rat HB-EGF, and inhibition of cell proliferation. DE10 also reacted with cells transfected with rat HB-EGF cDNA. Administration of 0.5 mg affinity-purified DE10 to normal rats did not cause significant albuminuria compared with controls. Five days after the induction of the acute PAN model, albuminuria was significantly greater in animals treated with 0.5 mg DE10 than a control mAb (162.6 +/- 32.4 vs. 64.8 +/- 10.2 mg/day, respectively, P < 0.01). Rats treated with DE10 had an earlier onset of severe albuminuria, but no increase in maximal albuminuria at later time points. Electron microscopy showed marked podocyte effacement in both DE10-treated and control animals, but no obvious difference between groups. However, adhesion of the human GEC line 56/10 A1 to laminin and fibronectin, but not to collagens I or IV, was reduced by DE10.'] Does inhibition of heparin-binding epidermal growth factor-like growth factor increase albuminuria in puromycin aminonucleoside nephrosis?