Inflammation-associated S100 proteins: new mechanisms that regulate function
- 6 March 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Amino Acids
- Vol. 41 (4), 821-842
- https://doi.org/10.1007/s00726-010-0528-0
Abstract
This review focuses on new aspects of extracellular roles of the calgranulins. S100A8, S100A9 and S100A12 are constitutively expressed in neutrophils and induced in several cell types. The S100A8 and S100A9 genes are regulated by pro- and anti-inflammatory mediators and their functions may depend on cell type, mediators within a particular inflammatory milieu, receptors involved in their recognition and their post-translational modification. The S100A8 gene induction in macrophages is dependent on IL-10 and potentiated by immunosuppressive agents. S100A8 and S100A9 are oxidized by peroxide, hypochlorite and nitric oxide (NO). HOCl generates intra-chain sulfinamide bonds; stronger oxidation promotes cross-linked forms that are seen in human atheroma. S100A8 is >200-fold more sensitive to oxidative cross-linking than low-density lipoprotein and may reduce oxidative damage. S100A8 and S100A9 can be S-nitrosylated. S100A8–SNO suppresses mast cell activation and inflammation in the microcirculation and may act as an NO transporter to regulate vessel tone in inflammatory lesions. S100A12 activates mast cells and is a monocyte and mast cell chemoattractant; a G-protein-coupled mechanism may be involved. Structure–function studies are discussed in relation to conservation and divergence of functions in S100A8. S100A12 induces cytokines in mast cells, but not monocytes/macrophages. It forms complexes with Zn2+ and, by chelating Zn2+, S100A12 significantly inhibits MMPs. Zn2+ in S100A12 complexes co-localize with MMP-9 in foam cells in atheroma. In summary, S100A12 has pro-inflammatory properties that are likely to be stable in an oxidative environment, because it lacks Cys and Met residues. Conversely, S100A8 and S100A9 oxidation and S-nitrosylation may have important protective mechanisms in inflammation.Keywords
This publication has 95 references indexed in Scilit:
- A review of the S100 proteins in cancerEuropean Journal of Surgical Oncology, 2008
- S100A9 mediates neutrophil adhesion to fibronectin through activation of β2 integrinsBiochemical and Biophysical Research Communications, 2007
- A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrinThe EMBO Journal, 2007
- Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasisNature, 2006
- S100A8 and S100A9 activate MAP kinase and NF-κB signaling pathways and trigger translocation of RAGE in human prostate cancer cellsExperimental Cell Research, 2006
- Alternative activation of macrophagesNature Reviews Immunology, 2003
- A Comparison of Human S100A12 with MRP-14 (S100A9)Biochemical and Biophysical Research Communications, 2000
- Ectodomain interactions of leukocyte integrins and pro-inflammatory GPI-linked membrane proteinsJournal of Pharmaceutical and Biomedical Analysis, 1997
- Novel Specific Chemotactic Receptor for S100L Protein on Guinea Pig EosinophilsBiochemical and Biophysical Research Communications, 1996
- Epidermal and dermal distribution of a myelomonocytic antigen (L1) shared by epithelial cells in various inflammatory skin diseasesJournal of the American Academy of Dermatology, 1986