PMID- 17634439
OWN - NLM
STAT- MEDLINE
DCOM- 20070926
LR  - 20171116
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 18
IP  - 8
DP  - 2007 Aug
TI  - Increased membrane expression of proteinase 3 during neutrophil adhesion in the 
      presence of anti proteinase 3 antibodies.
PG  - 2330-9
AB  - We investigated membrane proteinase 3 (mPR3) expression during TNF-alpha-induced 
      adhesion of neutrophils in the presence of anti-PR3 antibodies, a situation 
      occurring during anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated 
      vasculitis. Three increasing levels of mPR3 expression were observed on the 
      mPR3(+) neutrophil subset after stepwise cell activation. TNF-alpha activation 
      without adhesion, TNF-alpha-induced adhesion, and adhesion in the presence of 
      anti-PR3 mAb or human anti-PR3 ANCA resulted, respectively, in a two-, seven-, 
      and 24-fold increase of mPR3 levels. In plasma, anti-PR3 antibodies poorly 
      recognized suspended neutrophils, whereas they bound to mPR3 on adherent cells. 
      mPR3 upregulation was also triggered by IL-8, 
      formyl-methionyl-leucyl-phenylalanine (fMLP), and neutrophil adhesion to 
      activated human umbilical vein endothelial cells. It involved beta2 integrins and 
      Fcgamma receptor, because it was prevented by anti-CD18 antibodies and was not 
      observed with anti-PR3 F(ab')(2). Furthermore, it was specific to anti-PR3 mAb, 
      and no mPR3 upregulation was observed with anti-myeloperoxidase or anti-HLA-ABC 
      mAb. Newly expressed mPR3 molecules, after TNF-induced adhesion, were mobilized 
      from secretory vesicles (CD35(+)) and secondary granules (CD11b(+)). The 
      adhesion- and antibody-dependent upregulations of mPR3 expression occurred with 
      little azurophilic granule degranulation, no sign of apoptosis, and no further 
      CD177 upregulation. In conclusion, this study describes an amplifying loop in 
      polymorphonuclear neutrophil activation process, whereby ANCA are involved in the 
      membrane expression of their own antigen during cell adhesion. This could explain 
      the restriction of ANCA-associated vasculitis to small vessels, the main site of 
      neutrophil adhesion.
FAU - Brachemi, Soumeya
AU  - Brachemi S
AD  - INSERM U845, Universite Paris V Rene Descartes, France.
FAU - Mambole, Agnes
AU  - Mambole A
FAU - Fakhouri, Fadi
AU  - Fakhouri F
FAU - Mouthon, Luc
AU  - Mouthon L
FAU - Guillevin, Loic
AU  - Guillevin L
FAU - Lesavre, Philippe
AU  - Lesavre P
FAU - Halbwachs-Mecarelli, Lise
AU  - Halbwachs-Mecarelli L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070718
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (CD18 Antigens)
RN  - 0 (Interleukin-8)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 3.4.21.76 (Myeloblastin)
SB  - IM
MH  - Antibodies, Antineutrophil Cytoplasmic/blood/*immunology
MH  - Antibody Specificity
MH  - CD18 Antigens/metabolism
MH  - Cell Adhesion/drug effects/immunology
MH  - Cell Membrane/enzymology/immunology
MH  - Endothelium, Vascular/cytology/*immunology
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Myeloblastin/*immunology/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/cytology/*enzymology/immunology
MH  - Peroxidase/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Umbilical Veins/cytology
MH  - Up-Regulation/immunology
MH  - Vasculitis/*immunology/metabolism
EDAT- 2007/07/20 09:00
MHDA- 2007/09/27 09:00
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2007/09/27 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
AID - ASN.2006121309 [pii]
AID - 10.1681/ASN.2006121309 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2007 Aug;18(8):2330-9. doi: 10.1681/ASN.2006121309. Epub 2007 
      Jul 18.