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The role of proteinase 3 (PR3) and the protease-activated receptor-2 (PAR-2) pathway in dendritic cell (DC) maturation of human-DC-like monocytes and murine DC.

AbstractOBJECTIVES:
The aim of the study was to assess PAR-2 expression on dendritic cell (DC) subsets and other immune cells of Wegener's granulomatosis (WG) patients and healthy controls (HC) and to investigate whether Proteinase 3 (PR3, a serine protease which can activate PAR2) induces maturation of human DC-like monocytes and murine Flt-3 ligand- and GM-CSF-generated DC.
METHODS:
Human peripheral blood cells including DC subsets and Flt-3l- and GM-CSF-generated mouse DC were analysed for expression of PAR-2 and DC maturation markers by flow cytometry before and after stimulation with PR3, trypsin, PAR-2 agonist or LPS for 24 h.
RESULTS:
There was no difference of PAR-2 expression on PMNs, monocytes, lymphocytes and DC between all WG samples and HC. However, in inactive WG, expression of PAR-2 was downregulated on the cell surface of PMNs, monocytes, lymphocytes, and CD11c+DC compared to active WG and HC. PR3 and PAR2-agonists did not induce upregulation of PAR-2 or maturation markers of human DC-like monocytes in WG and HC. Likewise, murine PR3 did not induce upregulation of PAR-2 or maturation markers in murine DC.
CONCLUSIONS:
PAR-2 expression is downregulated on human peripheral blood cells including CD11c+ DC in inactive WG compared to active WG and HC, possibly reflecting a non-activated status of these cells in inactive disease. PR3 and PAR-2- agonists did not induce maturation of human ex vivo DC-like monocytes in WG and HC and of murine DC, suggesting this pathway is not singularly involved in the maturation of these cell subsets.
AuthorsBo Jiang, Evelin Grage-Griebenow, Elena Csernok, Kristine Butherus, Stefan Ehlers, Wolfgang L Gross, Julia U Holle
JournalClinical and experimental rheumatology (Clin Exp Rheumatol) 2010 Jan-Feb Vol. 28 Issue 1 Suppl 57 Pg. 56-61 ISSN: 0392-856X [Print] Italy
PMID20412704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CD11c Antigen
  • FCGR3B protein, human
  • Fcgr3 protein, mouse
  • GPI-Linked Proteins
  • Lipopolysaccharide Receptors
  • Receptor, PAR-2
  • Receptors, IgG
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Myeloblastin
Topics
  • Animals
  • Bone Marrow Cells (cytology, enzymology)
  • CD11c Antigen (metabolism)
  • Cell Differentiation (immunology)
  • Cells, Cultured
  • Dendritic Cells (cytology, enzymology)
  • Flow Cytometry
  • GPI-Linked Proteins
  • Granulomatosis with Polyangiitis (immunology, metabolism)
  • Humans
  • Lipopolysaccharide Receptors (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Monocytes (cytology, enzymology)
  • Myeloblastin (metabolism)
  • Receptor, PAR-2 (agonists, metabolism)
  • Receptors, IgG (metabolism)
  • Toll-Like Receptor 4 (metabolism)
  • Up-Regulation (immunology)

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