Reduced expression of C1q-mRNA in monocytes from patients with systemic lupus erythematosus

Published on Dec 1, 2006in Clinical and Experimental Immunology3.532
· DOI :10.1111/J.1365-2249.2006.03225.X
F Moosig2
Estimated H-index: 2
,
F Damm1
Estimated H-index: 1
+ 5 AuthorsJ O Schröder2
Estimated H-index: 2
Sources
Abstract
Inherited C1q deficiency is associated strongly with the development of systemic lupus erythematosus (SLE). The aim of our study was to evaluate the ability of monocytes from SLE patients without inherited C1q deficiency to up-regulate C1q-mRNA upon stimulation. Furthermore, we wanted to elucidate the physiological stimulus for up-regulation of C1q-mRNA. Peripheral blood mononuclear cell (PBMC)-derived monocytes from 10 SLE patients, 10 patients with rheumatoid arthritis (RA) and 10 healthy controls (HC) were stimulated with dexamethasone (DXM), interferon-gamma or both. Additionally, purified monocytes from HC were stimulated with interleukin (IL)-10. C1q-mRNA expression was measured by quantitative reverse transcription–polymerase chain reaction (RT–PCR). C1q protein was detected using the standard alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. SLE monocytes were significantly less able to up-regulate C1q-mRNA when compared to RA or HC. IL-10 was identified as an important stimulus for C1q synthesis. In SLE patients there is a significant functional impairment of monocytes to synthesize C1q upon stimulation. As C1q is linked to the process of recognition and removal of apoptotic cells, this relative C1q deficiency is likely to contribute to the reduced phagocytosis of apoptotic material observed in SLE and thereby might be a central pathogenetic factor.
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Background: Defects in phagocytosis of apoptotic cells have a role in the pathogenesis of autoimmune diseases. Decrease of phagocytosis of apoptotic cells occurs in systemic lupus erythematosus (SLE). Factors underlying this decrease are, presently, unknown. Objective: To analyse the expression of relevant membrane receptors of monocyte derived macrophages (MDM) from patients with SLE and assess their ability to phagocytose apoptotic cells in comparison with MDM from healthy controls. Additional...
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