title: Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux.
abstract: S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway. Chemotactic agents, cytokines, and particulate molecules were used to stimulate human neutrophils. MSU crystals, PMA, and H2O2 induced the release of S100A8, S100A9, and S100A12 homodimers, as well as S100A8/A9 heterodimer. High concentrations of S100A8/A9 and S100A12 were secreted in response to nanoparticles like MSU, silica, TiO2, fullerene, and single-wall carbon nanotubes as well as in response to microbe-derived molecules, such as zymosan or HKCA. However, neutrophils exposed to the chemotactic factors fMLP failed to secrete S100A8/A9 or S100A12. Secretion of S100A8/A9 was dependent on the production of reactive oxygen species and required K(+) exchanges through the ATP-sensitive K(+) channel. Altogether, these findings suggest that S100A12 and S100A8/A9 are secreted independently either via distinct mechanisms of secretion or following the activation of different signal transduction pathways.
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et L'immunologie, Centre de Recherche du CHU de Québec-Université Laval, and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Mélanie R
authors.initials: MR
authors.lastname: Tardif
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et L'immunologie, Centre de Recherche du CHU de Québec-Université Laval, and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Julie Andrea
authors.initials: JA
authors.lastname: Chapeton-Montes
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et L'immunologie, Centre de Recherche du CHU de Québec-Université Laval, and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Alma
authors.initials: A
authors.lastname: Posvandzic
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et L'immunologie, Centre de Recherche du CHU de Québec-Université Laval, and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pagé
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et L'immunologie, Centre de Recherche du CHU de Québec-Université Laval, and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gilbert
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et L'immunologie, Centre de Recherche du CHU de Québec-Université Laval, and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Tessier
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D040501:Calgranulin A / Q000737:chemistry / Q000378:metabolism*; D040502:Calgranulin B / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000067616:S100A12 Protein / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012822:Silicon Dioxide / Q000494:pharmacology; D014025:Titanium / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D016877:Oxidants; D017382:Reactive Oxygen Species; D000067616:S100A12 Protein; C090441:S100A12 protein, human; C009495:titanium dioxide; D014527:Uric Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012822:Silicon Dioxide; D006861:Hydrogen Peroxide; D014025:Titanium; D011188:Potassium