Granulocyte-macrophage colony-stimulating factor (GM-CSF) but not granulocyte colony-stimulating factor (G-CSF) induces plasma membrane expression ofproteinase 3 (PR3) on neutrophils in vitro

Citation
B. Hellmich et al., Granulocyte-macrophage colony-stimulating factor (GM-CSF) but not granulocyte colony-stimulating factor (G-CSF) induces plasma membrane expression ofproteinase 3 (PR3) on neutrophils in vitro, CLIN EXP IM, 120(2), 2000, pp. 392-398
Citations number
43
Categorie Soggetti
Immunology
Journal title
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
ISSN journal
00099104 → ACNP
Volume
120
Issue
2
Year of publication
2000
Pages
392 - 398
Database
ISI
SICI code
0009-9104(200005)120:2<392:GCF(BN>2.0.ZU;2-N
Abstract
The theoretical risk of triggering vasculitis resulting from administration of G-CSF and GM-CSF to patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), such as Wegener's granulomatosis (WG) , who develop agranulocytosis due to cytotoxic therapy, is unknown. Since t here is strong evidence that activation of polymorphonuclear neutrophils (P MN) induced by binding of ANCA to PR3 or myeloperoxidase (MPO) expressed on their plasma membrane is involved in the pathogenesis of systemic vasculit ides (SV), we studied the surface expression of PR3 and MPO on PMN from hea lthy donors in response to G-CSF and GM-CSF in vitro by flow cytometric ana lysis. Increasing doses of G-CSF did not alter PR3 expression on either unt reated or tumour necrosis factor-alpha (TNF-alpha)-primed donor PMN signifi cantly. In contrast, GM-CSF significantly increased PR3 membrane expression on both intact PMN and neutrophils primed with TNF-alpha. MPO expression w as not significantly altered by either G-CSF or GM-CSF. In summary, these d ata demonstrate that GM-CSF, but not G-CSF, induces plasma membrane express ion of PR3 on PMN in vitro. Since in AAV accessibility of the antigen (PR3 or MPO) to the antibody (ANCA) on the plasma membrane of PMN is thought to be essential for neutrophil activation by ANCA, the results of the present study suggest that administration of GM-CSF to patients with WG with neutro penia implies a definite theoretical risk of deterioration of vasculitis vi a this mechanism.