PMID- 11316851
OWN - NLM
STAT- MEDLINE
DCOM- 20010809
LR  - 20210511
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 12
IP  - 5
DP  - 2001 May
TI  - Proteinase 3 enhances endothelial monocyte chemoattractant protein-1 production 
      and induces increased adhesion of neutrophils to endothelial cells by 
      upregulating intercellular cell adhesion molecule-1.
PG  - 932-940
LID - 10.1681/ASN.V125932 [doi]
AB  - Wegener's granulomatosis is an autoimmune disease that is characterized by 
      systemic vasculitis and granuloma formation. Early influx of polymorphonuclear 
      neutrophils (PMN), followed at a later stage by mononuclear cells, contributes to 
      the granulomatous inflammation. Previous studies have shown that proteinase 3 
      (PR3), the major autoantigen in Wegener's granulomatosis, specifically binds to 
      endothelial cells and plays a possible role in activation of these cells by 
      enhancing interleukin-8 production, thus providing a chemotactic and activating 
      stimulus for PMN. The present study demonstrated that PR3 enhances the production 
      of monocyte chemoattractant protein-1 (MCP-1) by human umbilical vein endothelial 
      cells (HUVEC) in a dose- and time-dependent manner. The PR3-induced increase in 
      MCP-1 production was demonstrated at both the protein and the mRNA levels and was 
      chemotactic for monocytes. In addition, it was demonstrated that PR3 induces a 
      dose- and time-dependent increase in the expression of intercellular adhesion 
      molecule-1 (ICAM-1) as determined by fluorescence-activated cell sorter analysis. 
      The PR3-induced increase in expression of ICAM-1 was also demonstrated at the 
      mRNA level. PR3 induced a slight increase in vascular cell adhesion molecule-1 
      expression and had no effect on the expression of both P- and E-selectin. 
      Incubation of HUVEC for 24 h in the presence of PR3 resulted in a significant 
      increase in adhesion of PMN, which was reduced to baseline levels in the presence 
      of blocking monoclonal antibody anti-ICAM-1 or anti-CD18 or a combination of 
      both. Monocytes showed a slight but statistically not significant increase in 
      adhesion. Incubation of HUVEC with PR3 for 4 h did not result in enhanced 
      adhesion of either PMN or monocytes. It was hypothesized that PR3, which may be 
      released locally at inflammatory sites after activation of cytokine primed PMN, 
      plays a role in endothelial cell activation by enhancing both interleukin-8 and 
      MCP-1 production, thus providing a chemotactic and activating stimulus for both 
      PMN and monocytes. In addition, PR3 may contribute to the ongoing inflammation by 
      enhancing the adhesion of PMN to endothelial cells by upregulating ICAM-1 
      expression.
FAU - Taekema-Roelvink, Miriam E J
AU  - Taekema-Roelvink MEJ
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Kooten, Cees VAN
AU  - Kooten CV
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Kooij, Sandra VAN DER
AU  - Kooij SV
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Heemskerk, Evert
AU  - Heemskerk E
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Daha, Mohamed R
AU  - Daha MR
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Messenger)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.76 (Myeloblastin)
SB  - IM
MH  - Base Sequence
MH  - Cell Adhesion
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - DNA Primers/genetics
MH  - Endothelium, Vascular/cytology/drug effects/metabolism
MH  - Granulomatosis with Polyangiitis/etiology/genetics/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Intercellular Adhesion Molecule-1/genetics/*metabolism
MH  - Monocytes/cytology/drug effects/metabolism
MH  - Myeloblastin
MH  - Neutrophils/*cytology/drug effects/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Serine Endopeptidases/*metabolism/pharmacology
MH  - Up-Regulation
EDAT- 2001/04/24 10:00
MHDA- 2001/08/10 10:01
CRDT- 2001/04/24 10:00
PHST- 2001/04/24 10:00 [pubmed]
PHST- 2001/08/10 10:01 [medline]
PHST- 2001/04/24 10:00 [entrez]
AID - 12/5/932 [pii]
AID - 10.1681/ASN.V125932 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2001 May;12(5):932-940. doi: 10.1681/ASN.V125932.