Journal
CELL AND TISSUE RESEARCH
Volume 351, Issue 1, Pages 139-148Publisher
SPRINGER
DOI: 10.1007/s00441-012-1508-3
Keywords
Soluble RAGE; Inflammation; Mac-1(+) cells; B cells; Mouse (NMRI)
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Funding
- Gothenburg Medical Society
- Swedish Medical Society
- Swedish Association against Rheumatism
- Gothenburg Association against Rheumatism
- King Gustaf V foundation
- Rune and Ulla Almlovs Foundation
- Family Tholens and Kristlers Foundation
- Nanna Svartz Foundation
- Apotekare Hedberg Foundation
- Magnus Bergwall Foundation
- Lundberg Foundation
- University of Gothenburg
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Receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that binds a variety of pro-inflammatory ligands. Its soluble form, sRAGE, can compete for ligand binding and thereby have an anti-inflammatory effect. We have recently reported that sRAGE also exerts pro-inflammatory and chemotactic properties suggesting a dual role for sRAGE in immune modulation. Our present aim was to analyse the immunomodulatory properties of sRAGE in vivo with respect to acquired immunity. Naive mice were treated intra-peritoneally with sRAGE and cells from peritoneal lavage, spleens and bone marrow were examined. Mice treated with sRAGE displayed an increased leucocyte count in the peritoneal cavity, enlarged spleens and increased cellularity compared with vehicle-treated animals. Furthermore, sRAGE-treated mice had a significantly increased frequency and number of CD19(+) B cells in spleen and a reduced frequency of CD19(+) B cells in bone marrow compared with controls. Functionally, splenocytes from sRAGE-treated mice showed elevated IgG production and up to a four-fold increased IgM secretion compared with control animals and produced significantly higher levels of interleukin-10, interferon-gamma and interleukin-6 in response to lipopolysaccharide stimulation. Our results suggest that sRAGE has immunomodulatory properties, since intra-peritoneal administration of sRAGE into healthy mice leads to rearrangements in cellular composition in the bone marrow and spleen. Moreover, the administration of sRAGE directs B cells into the spleen and towards differentiation. Our novel findings indicate that sRAGE exerts an effect on the cells of adaptive immunity.
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