Trends in Immunology
Research focusPhagocyte-specific S100 proteins: a novel group of proinflammatory molecules
Section snippets
S100A8 and S100A9 and phagocyte activation
The initial description of S100A8 and S100A9 already suggested that these proteins are involved in phagocyte biology during inflammation [2]. They attracted major interest in view of their high cytosolic concentration and their high intracellular calcium-binding capacity in phagocytes [3]. Targeted deletion of S100A8 in mice is incompatible with life owing to rapid resorption of homozygous null embryos by day 9.5. It is not clear whether abnormalities in migration of embryonic cells or
Overexpression of S100A8 and S100A9 defines a novel inflammatory disorder
The particular relevance of S100A8 and S100A9 for inflammation has been underlined by identification of a new inflammatory disorder just described, whose hallmark is an extraordinarily high abundance of these two molecules. This novel disease is characterized by recurrent infections, hepatosplenomegaly, anaemia, cutaneous vasculitis and evidence of systemic inflammation [17]. As a result of the zinc-binding properties of S100A8 and S100A9, which might be mediated by a hexxh motif also found in
S100A12–RAGE interaction: a novel inflammatory signal pathway
S100A12 has extensive homology with S100A8 and S100A9 at protein and DNA level, but does not interact with either of these proteins, and thus has a distinct role during inflammation [19]. Similar to S100A8 and S100A9, S100A12 is secreted by activated human neutrophils [20]. The interaction of S100A12 with the receptor for advanced glycation end products (RAGE) revealed the first plausible receptor–ligand model for an S100 protein [21] (Fig. 2). RAGE is expressed on macrophages, lymphocytes and
Conclusion
Recently published data provide growing evidence that S100A8, S100A9 and S100A12 comprise a new group of proinflammatory proteins expressed by phagocytes, which are attractive targets for novel diagnostic and therapeutic approaches to manipulate the innate immune system in inflammatory diseases.
Acknowledgements
The ribbon model of the S100A8–S100A9 heterodimer was kindly provided by G. Fritz, University of Zürich, Switzerland.
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