Staphylococcal acid phosphatase binds to endothelial cells via charge interaction; a pathogenic role in Wegener's granulomatosis?

The majority of patients with Wegener's granulomatosis (WG) are chronic nas al carriers of Staphylococcus aureus. Chronic nasal carriage of S. aureus i s associated with an increased risk of developing a relapse of the disease. The mechanism by which this occurs is still unknown. We hypothesized that a cationic protein of S. aureus, staphylococcal acid phosphatase (SAcP), ac ts as a planted antigen and initiates glomerulonephritis and vasculitis in patients with WG. In order to test the hypothesis that SAcP can act as a pl anted antigen in WG, we studied the ability of SAcP to bind to human umbili cal vein endothelial cells (HUVEC) and human glomerular endothelial cells. We also studied whether this binding can be prevented by preincubation with an anionic protein, and whether binding of SAcP activates endothelial cell s. We also evaluated whether antibodies in sera of patients with WG are abl e to bind to endothelial cell-bound SAcP. The results show that SAcP can ac t as a planted antigen by binding to both types of endothelial cells in a c oncentration-dependent manner. Binding of concentrations as low as 4 mu g/m l can be detected on HUVEC within 5 min of incubation. Binding of SAcP to e ndothelial cells was charge-dependent but did not activate endothelial cell s. Finally, endothelial cell-bound SAcP was recognized by sera of patients with WG. The data suggest a possible pathogenic role for SAcP by acting as a planted antigen thereby initiating glomerulonephritis and vasculitis in p atients with WG.