Document Detail


Damage-associated molecular pattern S100A9 increases bactericidal activity of human neutrophils by enhancing phagocytosis.
MedLine Citation:
PMID:  21325622     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jean-Christophe Simard; Marie-Michelle Simon; Philippe A Tessier; Denis Girard
Publication Detail:
Type:  Journal Article     Date:  2011-02-16
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-03     Completed Date:  2011-05-26     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3622-31     Citation Subset:  AIM; IM    
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.
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MeSH Terms
Descriptor/Qualifier:
Blood Bactericidal Activity / immunology*
Calgranulin B / physiology*
Enzyme Activation / immunology
Escherichia coli / immunology,  metabolism
Host-Pathogen Interactions / immunology
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Neutrophils / enzymology,  immunology*,  microbiology*
Phagocytosis / immunology*
Phosphatidylinositol 3-Kinases / metabolism
Protein-Tyrosine Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Reactive Oxygen Species / metabolism
Receptors, Pattern Recognition / physiology*
Chemical
Reg. No./Substance:
0/Calgranulin B; 0/Intracellular Signaling Peptides and Proteins; 0/Reactive Oxygen Species; 0/Receptors, Pattern Recognition; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Syk kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3

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