The calcium-binding protein S100A12 induces neutrophil adhesion, migration, and release from bone marrow in mouse at concentrations similar to those found in human inflammatory arthritis.
We investigated the proinflammatory activities of S100A12 in the context of synovial inflammation. S100A12 levels were increased in the synovial fluids and plasma of patients with gout, rheumatoid arthritis, psoriatic arthritis, and undetectable in osteoarthritis, a noninflammatory disorder. S100A12 proved to induce neutrophil adhesion to fibrinogen via Mac-1 at concentrations similar to those found in the synovial fluids. Similar concentrations induced the recruitment of large numbers of neutrophils and monocytes in the murine air pouch model. To characterize the effect of increased S100A12 plasma levels, mice were injected intravenously with S100A12. This led to the mobilization of neutrophils from the bone marrow to the peripheral blood. These results suggest that S100A12 stimulates the accumulation of neutrophil by inducing their release from the bone marrow, as well as by activating their adhesion and migration toward inflammatory sites.
Infectious Diseases Research Center, Laval University Hospital Center, 2705 Laurier Boulevard, Sainte-Foy, Quebec, Canada G1V 4G2.
Pascal
P
Rouleau
Karen
K
Vandal
Carle
C
Ryckman
Patrice E
PE
Poubelle
Annie
A
Boivin
Mariève
M
Talbot
Philippe A
PA
Tessier
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054407:Chemokine CCL4; D002633:Chemotaxis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011817:Rabbits; D051381:Rats; D009418:S100 Proteins; D000067616:S100A12 Protein; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology
D002135:Calcium-Binding Proteins; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human