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Open Access Research article

Protein synthesis of the pro-inflammatory S100A8/A9 complex in plasmacytoid dendritic cells and cell surface S100A8/A9 on leukocyte subpopulations in systemic lupus erythematosus

Christian Lood12*, Martin Stenström3, Helena Tydén2, Birgitta Gullstrand1, Eva Källberg3, Tomas Leanderson3, Lennart Truedsson1, Gunnar Sturfelt2, Fredrik Ivars3 and Anders A Bengtsson2

Author Affiliations

1 Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Sölvegatan 23, 223 62 Lund, Sweden

2 Department of Clinical Sciences, Section of Rheumatology, Lund University and Skåne University Hospital, Kioskgatan 3, 221 85 Lund, Sweden

3 Department of Experimental Medical Science, Immunology Group, Lund University, Sölvegatan 19, 221 84 Lund, Sweden

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Arthritis Research & Therapy 2011, 13:R60  doi:10.1186/ar3314

Published: 14 April 2011

Abstract

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in many different organ systems, activation of leukocytes and production of pro-inflammatory cytokines. The heterodimer of the cytosolic calcium-binding proteins S100A8 and S100A9 (S100A8/A9) is secreted by activated polymorphonuclear neutrophils (PMNs) and monocytes and serves as a serum marker for several inflammatory diseases. Furthermore, S100A8 and S100A9 have many pro-inflammatory properties such as binding to Toll-like receptor 4 (TLR4). In this study we investigated if aberrant cell surface S100A8/A9 could be seen in SLE and if plasmacytoid dendritic cells (pDCs) could synthesize S100A8/A9.

Methods

Flow cytometry, confocal microscopy and real-time PCR of flow cytometry-sorted cells were used to measure cell surface S100A8/A9, intracellular S100A8/A9 and mRNA levels of S100A8 and S100A9, respectively.

Results

Cell surface S100A8/A9 was detected on all leukocyte subpopulations investigated except for T cells. By confocal microscopy, real-time PCR and stimulation assays, we could demonstrate that pDCs, monocytes and PMNs could synthesize S100A8/A9. Furthermore, pDC cell surface S100A8/A9 was higher in patients with active disease as compared to patients with inactive disease. Upon immune complex stimulation, pDCs up-regulated the cell surface S100A8/A9. SLE patients had also increased serum levels of S100A8/A9.

Conclusions

Patients with SLE had increased cell surface S100A8/A9, which could be important in amplification and persistence of inflammation. Importantly, pDCs were able to synthesize S100A8/A9 proteins and up-regulate the cell surface expression upon immune complex-stimulation. Thus, S100A8/A9 may be a potent target for treatment of inflammatory diseases such as SLE.