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

• Published in: The Journal of immunology (1950) Vol. 170; no. 6; pp. 3233 - 3242
• Main Authors: Ryckman, Carle, Vandal, Karen, Rouleau, Pascal, Talbot, Marieve, Tessier, Philippe A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.03.2003
• 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.6.3233

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.