Blockade of S100A8 and S100A9 suppresses neutrophil migration in response to lipopolysaccharide.
Recently, proinflammatory activities had been described for S100A8 and S100A9, two proteins found at inflammatory sites and within the neutrophil cytoplasm. In this study, we investigated the role of these proteins in neutrophil migration in vivo in response to LPS. LPS was injected into the murine air pouch, which led to the release of S100A8, S100A9, and S100A8/A9 in the pouch exudates that preceded accumulation of neutrophils. Passive immunization against S100A8 and S100A9 led to a 52% inhibition of neutrophil migration in response to LPS at 3 h postinjection. Injection of LPS was also associated with an increase in peripheral blood neutrophils and the presence in serum of S100A9 and S100A8/A9. Intravenous injection of S100A8, S100A9, or S100A8/A9 augmented the number of circulating neutrophils and diminished the number of neutrophils in the bone marrow, demonstrating that S100A8 and S100A9 induced the mobilization of neutrophils from the bone marrow to the blood. Finally, passive immunization with anti-S100A9 inhibited the neutrophilia associated with LPS injection in the air pouch. These results suggest that S100A8 and S100A9 play a role in the inflammatory response to LPS by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site.
Vandal
Karen
K
Centre de Recherche en Infectiologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, 2705 Boulevard Laurier, Sainte-Foy, Québec, Canada G1V 4G2.
Rouleau
Pascal
P
Boivin
Annie
A
Ryckman
Carle
C
Talbot
Mariève
M
Tessier
Philippe A
PA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D040501:Calgranulin A / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D040502:Calgranulin B / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002449:Cell Aggregation / Q000276:immunology; D002464:Cell Migration Inhibition; D019281:Dimerization; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007964:Leukocytosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
D040501:Calgranulin A; D040502:Calgranulin B; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011994:Recombinant Proteins