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 nasal carriers of Staphylococcus aureus. Chronic nasal carriage of S. aureus is 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), acts 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 planted antigen in WG, we studied the ability of SAcP to bind to human umbilical 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 cells. We also evaluated whether antibodies in sera of patients with WG are able to bind to endothelial cell-bound SAcP. The results show that SAcP can act as a planted antigen by binding to both types of endothelial cells in a concentration-dependent manner. Binding of concentrations as low as 4 microg/ml can be detected on HUVEC within 5 min of incubation. Binding of SAcP to endothelial cells was charge-dependent but did not activate endothelial cells. 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 patients with WG.
Brons
R H
RH
Department of Clinical Immunology and Medical Microbiology, University Hospital Groningen, Groningen, The Netherlands.
Bakker
H I
HI
Van Wijk
R T
RT
Van Dijk
N W
NW
Muller Kobold
A C
AC
Limburg
P C
PC
Manson
W L
WL
Kallenberg
C G
CG
Tervaert
J W
JW
D000135:Acid Phosphatase / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000382:microbiology*; D014890:Granulomatosis with Polyangiitis / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology*; D006801:Humans; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000201:enzymology*
D000135:Acid Phosphatase