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 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.
Ryckman
Carle
C
Infectious Diseases Research Center, Laval University Hospital Center, Sainte-Foy, Quebec, Canada.
Vandal
Karen
K
Rouleau
Pascal
P
Talbot
Mariève
M
Tessier
Philippe A
PA
D000328:Adult; D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D040501:Calgranulin A / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D040502:Calgranulin B / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002630:Chemotactic Factors / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D019281:Dimerization; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology*; D007279:Injections, Subcutaneous; D039302:Integrin alphaVbeta3 / Q000502:physiology; D019041:L-Selectin / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D015854:Up-Regulation / Q000502:physiology
D039481:CD11b Antigen; D040501:Calgranulin A; D040502:Calgranulin B; D002630:Chemotactic Factors; D018836:Inflammation Mediators; D039302:Integrin alphaVbeta3; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D019041:L-Selectin; D005340:Fibrinogen; D002118:Calcium