title: S100A8/A9: From basic science to clinical application.
abstract: Neutrophils and monocytes belong to the first line of immune defence cells and are recruited to sites of inflammation during infection or sterile injury. Both cells contain huge amounts of the heterodimeric protein S100A8/A9 in their cytoplasm. S100A8/A9 belongs to the Ca2+binding S100 protein family and has recently gained a lot of interest as a critical alarmin modulating the inflammatory response after its release (extracellular S100A8/A9) from neutrophils and monocytes. Extracellular S100A8/A9 interacts with the pattern recognition receptors Toll-like receptor 4 (TLR4) and Receptor for Advanced Glycation Endproducts (RAGE) promoting cell activation and recruitment. Besides its biological function, S100A8/A9 (also known as myeloid related protein 8/14, MRP8/14) was identified as interesting biomarker to monitor disease activity in chronic inflammatory disorders including inflammatory bowel disease and rheumatoid arthritis. Furthermore, S100A8/A9 has been tested successfully in pre-clinical imaging studies to localize sites of infection or sterile injury. Finally, recent evidence using small molecule inhibitors for S100A8/A9 also suggests that blocking S100A8/A9 activity exerts beneficial effects on disease activity in animal models of autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease. This review will provide a comprehensive and detailed overview into the structure and biological function of S100A8/A9 and also will give an outlook in terms of diagnostic and therapeutic applications targeting S100A8/A9.
authors: Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors: Monika
authors: M
authors: Pruenster
authors: Institute of Immunology, University of Muenster, Muenster, Germany.
authors: Thomas
authors: T
authors: Vogl
authors: Institute of Immunology, University of Muenster, Muenster, Germany.
authors: Johannes
authors: J
authors: Roth
authors: Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany. Electronic address: markus.sperandio@lmu.de.
authors: Markus
authors: M
authors: Sperandio
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D040501:Calgranulin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D040502:Calgranulin B / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D058990:Molecular Targeted Therapy; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D000067759:Receptor for Advanced Glycation End Products; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D002118:Calcium