PMID- 12773517
OWN - NLM
STAT- MEDLINE
DCOM- 20030626
LR  - 20190605
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 73
IP  - 6
DP  - 2003 Jun
TI  - Expression of myeloperoxidase (MPO) by neutrophils is necessary for their 
      activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO.
PG  - 841-9
AB  - Anti-neutrophil cytoplasm autoantibodies (ANCA) directed against proteinase-3 and 
      myeloperoxidase (MPO) activate tumor necrosis factor-alpha-primed neutrophils in 
      vitro. We used neutrophils from one completely and one partially MPO-deficient 
      donor to assess the requirement of MPO expression for neutrophil activation by 
      anti-MPO antibodies. The MPO deficiencies were defined enzymatically, by 
      immunocytochemistry and by immunoblotting. The mutations in the MPO genes of 
      these donors were identified as a combination of a novel splice-site mutation at 
      the 3' end of intron 11 (A-2-->C), a deletion of 14 nucleotides in exon 9 
      (A1555-C1568), and a novel C1907 --> T (636Thr-->Met) substitution in exon 11 in 
      the completely MPO-deficient donor and as the same splice-site mutation and a 
      novel C995 --> T (332Ala-->Val) substitution in exon 7 in the partially 
      MPO-deficient donor. Monoclonal antibody 4.15 against MPO and 
      MPO-ANCA-immunoglobulin G induced no superoxide anion production in these 
      MPO-deficient neutrophils despite a normal production induced by other stimuli. 
      Thus, the presence of MPO is a conditio sine qua non for neutrophil activation by 
      anti-MPO antibodies. Moreover, we demonstrated that by means of these 
      MPO-deficient cells, hydrogen peroxide may diffuse from neutrophils to 
      surrounding cells, which may contribute to the damage induced by oxygen radicals 
      in the pathology of systemic vasculitides.
FAU - Reumaux, Dominique
AU  - Reumaux D
AD  - Departement d'Hematologie-Immunologie-Cytogenetique, Centre Hospitalier de 
      Valenciennes, France. reumaux-d@ch-valenciennes.fr
FAU - de Boer, Martin
AU  - de Boer M
FAU - Meijer, Alexander B
AU  - Meijer AB
FAU - Duthilleul, Patrick
AU  - Duthilleul P
FAU - Roos, Dirk
AU  - Roos D
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Peptides)
RN  - 11062-77-4 (Superoxides)
RN  - 1N3CZ14C5O (Rhodamine 123)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Antibodies, Antineutrophil Cytoplasmic/*pharmacology
MH  - Cell Adhesion
MH  - DNA Mutational Analysis
MH  - Diffusion
MH  - Fluorescent Dyes
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - *Neutrophil Activation
MH  - Neutrophils/*enzymology/immunology
MH  - Peptides/analysis
MH  - Peroxidase/deficiency/genetics/*immunology/metabolism
MH  - Rhodamine 123
MH  - Superoxides/metabolism
EDAT- 2003/05/30 05:00
MHDA- 2003/06/27 05:00
CRDT- 2003/05/30 05:00
PHST- 2003/05/30 05:00 [pubmed]
PHST- 2003/06/27 05:00 [medline]
PHST- 2003/05/30 05:00 [entrez]
AID - 10.1189/jlb.1102567 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2003 Jun;73(6):841-9. doi: 10.1189/jlb.1102567.