title: Damage-associated molecular pattern S100A9 increases bactericidal activity of human neutrophils by enhancing phagocytosis.
abstract: The damage-associated molecular-pattern S100A9 is found at inflammatory sites in infections and various autoimmune diseases. It is released at very high concentrations in the extracellular milieu by activated neutrophils and monocytes in response to various agents. This proinflammatory protein is found in infected mucosae and tissue abscesses where it acts notably as a potent neutrophil activator. In this study, we examined the role of S100A9 in the control of infections. S100A9 was found to increase human neutrophil bactericidal activity toward Escherichia coli. Although S100A9 induced the accumulation of reactive oxygen species over time through the activation of NADPH oxidase, its antimicrobial activity was mediated mainly by enhancing the efficiency of neutrophil phagocytosis. Interestingly, S100A9 did not act by increasing cell surface expression of CD16, CD32, or CD64 in neutrophils, indicating that its biological effect in FcR-mediated phagocytosis is independent of upregulation of FcγR levels. However, S100A9-induced phagocytic activity required the phosphorylation of Erk1/2, Akt, and Syk. Taken together, our results demonstrate that S100A9 stimulates neutrophil microbicidal activity by promoting phagocytosis.
authors.affiliation: Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Québec City, Québec H7V 1B7, Canada.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Simard
authors.forename: Marie-Michelle
authors.initials: MM
authors.lastname: Simon
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Tessier
authors.forename: Denis
authors.initials: D
authors.lastname: Girard
mesh_terms: D001770:Blood Bactericidal Activity / Q000276:immunology*; D040502:Calgranulin B / Q000502:physiology*; D004789:Enzyme Activation / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*; D010587:Phagocytosis / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000502:physiology*; D000072377:Syk Kinase
chemical_list: D040502:Calgranulin B; D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D051192:Receptors, Pattern Recognition; D000072377:Syk Kinase; C000606896:SYK protein, human; C535150:MAPK1 protein, human