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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.
- Source :
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Clinical and experimental rheumatology [Clin Exp Rheumatol] 2010 Jan-Feb; Vol. 28 (1 Suppl 57), pp. 56-61. - Publication Year :
- 2010
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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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Bone Marrow Cells cytology
Bone Marrow Cells enzymology
CD11c Antigen metabolism
Cell Differentiation immunology
Cells, Cultured
Dendritic Cells cytology
Flow Cytometry
GPI-Linked Proteins
Granulomatosis with Polyangiitis immunology
Humans
Lipopolysaccharide Receptors metabolism
Mice
Mice, Inbred C57BL
Monocytes cytology
Receptor, PAR-2 agonists
Receptors, IgG metabolism
Toll-Like Receptor 4 metabolism
Up-Regulation immunology
Dendritic Cells enzymology
Granulomatosis with Polyangiitis metabolism
Monocytes enzymology
Myeloblastin metabolism
Receptor, PAR-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0392-856X
- Volume :
- 28
- Issue :
- 1 Suppl 57
- Database :
- MEDLINE
- Journal :
- Clinical and experimental rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 20412704