Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion

S100A8 and S100A9 are small calcium-binding proteins that are highly expressed in neutrophil and monocyte cytosol and are found at high levels in the extracellular milieu during inflammatory conditions. Although reports have proposed a proinflammatory role for these proteins, their extracellular act...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2003-03, Vol.170 (6), p.3233-3242
Main Authors: Ryckman, Carle, Vandal, Karen, Rouleau, Pascal, Talbot, Marieve, Tessier, Philippe A
Format: Article
Language:English
Subjects:
Adult
Animals
Calcium - metabolism
Calgranulin A - administration & dosage
Calgranulin A - biosynthesis
Calgranulin A - physiology
Calgranulin B - administration & dosage
Calgranulin B - biosynthesis
Calgranulin B - physiology
CD11b Antigen - biosynthesis
CD11b Antigen - metabolism
Cell Adhesion - physiology
Chemotactic Factors - administration & dosage
Chemotactic Factors - biosynthesis
Chemotactic Factors - physiology
Chemotaxis, Leukocyte - physiology
Dimerization
Female
Fibrinogen - metabolism
Genetic Vectors
Humans
Inflammation Mediators - administration & dosage
Inflammation Mediators - physiology
Injections, Subcutaneous
Integrin alphaVbeta3 - physiology
L-Selectin - metabolism
Macrophage-1 Antigen - biosynthesis
Macrophage-1 Antigen - metabolism
Macrophage-1 Antigen - physiology
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Neutrophil Infiltration - physiology
Neutrophils - metabolism
Neutrophils - physiology
Protein Binding - physiology
Recombinant Proteins - biosynthesis
Up-Regulation - physiology
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Summary:S100A8 and S100A9 are small calcium-binding proteins that are highly expressed in neutrophil and monocyte cytosol and are found at high levels in the extracellular milieu during inflammatory conditions. Although reports have proposed a proinflammatory role for these proteins, their extracellular activity remains controversial. In this study, we report that S100A8, S100A9, and S100A8/A9 caused neutrophil chemotaxis at concentrations of 10(-12)-10(-9) M. S100A8, S100A9, and S100A8/A9 stimulated shedding of L-selectin, up-regulated and activated Mac-1, and induced neutrophil adhesion to fibrinogen in vitro. Neutralization with Ab showed that this adhesion was mediated by Mac-1. Neutrophil adhesion was also associated with an increase in intracellular calcium levels. However, neutrophil activation by S100A8, S100A9, and S100A8/A9 did not induce actin polymerization. Finally, injection of S100A8, S100A9, or S100A8/A9 into a murine air pouch model led to rapid, transient accumulation of neutrophils confirming their activities in vivo. These studies 1) show that S100A8, S100A9, and S100A8/A9 are potent stimulators of neutrophils and 2) strongly suggest that these proteins are involved in neutrophil migration to inflammatory sites.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.170.6.3233