Type

Journal Article

Authors

S J O'Neill
N G McElvaney
R Coakley
C Taggart
C P Rooney

Subjects

Microbiology

Topics
male aged serine endopeptidases wegener granulomatosis drug effects proteinase inhibitory proteins secretory alpha 1 antitrypsin humans middle aged adult pharmacology respiratory burst etiology neutrophil activation female immunoglobulin g immunology proteins tumor necrosis factor alpha metabolism serine proteinase inhibitors myeloblastin antibodies antineutrophil cytoplasmic

Anti-proteinase 3 antibody activation of neutrophils can be inhibited by alpha1-antitrypsin. (2001)

Abstract Wegener's granulomatosis (WG) is classically associated with the presence of cytoplasmic antineutrophil cytoplasmic autoantibodies (c-ANCA). Proteinase 3 (PR3), the target antigen for c-ANCA, is inhibited by the antiprotease alpha1-antitrypsin (A1AT), and recent studies have demonstrated that WG patients who are A1AT-deficient have a worse clinical course, suggesting that a protease-antiprotease imbalance may play a role in WG. We evaluated the effect of A1AT on anti-PR3 antibody-induced activation of neutrophils. The neutrophil was chosen because of its central role in the pathogenesis of WG. Isolated neutrophils from healthy controls were incubated with tumor necrosis factor (TNF)-alpha to induce surface expression of PR3. Subsequently, they were stimulated with a monoclonal antibody to PR3, resulting in a significant increase in respiratory burst. Addition of A1AT (1 mg/ml) to the TNF-alpha- primed cells before the addition of the anti-PR3 antibody resulted in a 47% reduction in anti-PR3 antibody-induced activation. A1AT mediated this inhibitory action by preventing anti-PR3 antibody binding to PR3 on the cell, thereby preventing the PR3-FcgammaR11a cross-linkage required for cell activation. Further, anti-PR3 antibody-induced activation of neutrophils from WG patients can be reduced by 56% with A1AT. These data suggest that protease-antiprotease interactions may play a pivotal role in neutrophil activation in WG.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

S J O'Neill, N G McElvaney, R Coakley, C Taggart, C P Rooney

Experts in our system

1
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
2
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
3
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54