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The exact outcome of their extracellular function depends on the local tissue environment in which they are released; both anti-inflammatory and pro-inflammatory responses are described, modulating the immune system by binding Toll-like receptor (TLR)-4 or the receptor for advanced glycation end-products (RAGE). However, the contribution of the proteins in the pathophysiology of chronic rhinosinusitis (CRS) remains unclear.<\/jats:p><jats:p>Homomeric S100A8 and S100A9, and heteromeric S100A8\/A9 proteins were evaluated in CRS with\/without nasal polyps (CRSw\/sNP) and controls. Functional responses were assessed in polyp tissue stimulated with S100 proteins in the presence of TLR-4 and RAGE blocking antibodies.<\/jats:p><jats:p>S100A8, S100A9 and S100A8\/A9 protein levels were significantly higher in CRSwNP patients, showing increased deposition on extracellular matrix (ECM) structures of CRSwNP tissue in contrast to CRSsNP and controls. In the presence of<jats:italic>Staphylococcus aureus<\/jats:italic>, S100A8\/A9 is released from neutrophils and from the ECM. Extracellular S100A8 and S100A9 proteins induced increased levels of diverse inflammatory mediators<jats:italic>via<\/jats:italic>TLR-4 engagement.<\/jats:p><jats:p>The inflammatory\/remodelling characteristics of CRSwNP specifically allow increased retention of S100A8, S100A9 and S100A8\/A9 proteins in the ECM of CRSwNP tissue. Upon release, homodimeric proteins act as a local danger signal inducing inflammatory mediators, predominantly<jats:italic>via<\/jats:italic>TLR-4 activation.<\/jats:p>","DOI":"10.1183\/13993003.00159-2015","type":"journal-article","created":{"date-parts":[[2015,10,26]],"date-time":"2015-10-26T18:42:18Z","timestamp":1445884938000},"page":"264-274","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":51,"title":["Differential release and deposition of S100A8\/A9 proteins in inflamed upper airway tissue"],"prefix":"10.1183","volume":"47","author":[{"given":"Koen","family":"Van 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