Abstract | OBJECTIVES: 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.
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Authors | Bo Jiang, Evelin Grage-Griebenow, Elena Csernok, Kristine Butherus, Stefan Ehlers, Wolfgang L Gross, Julia U Holle |
Journal | Clinical and experimental rheumatology
(Clin Exp Rheumatol)
2010 Jan-Feb
Vol. 28
Issue 1 Suppl 57
Pg. 56-61
ISSN: 0392-856X [Print] Italy |
PMID | 20412704
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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