Abstract
S100 proteins represent a new class of chemoattractants. Here we extend earlier evidence for the proinflammatory properties of human S100A12. A12 induced migration of monocytoid cells, with optimal activity at 10(-10) M and potency of >10(-9) M C5a. Neutrophils were poorly responsive, and lymphocyte migration was not affected. Actin polymerization in monocytoid cells was accompanied by a sustained [Ca(2+)]i flux of a magnitude comparable with C5a. A12 elicited a transient infiltration of neutrophils (4-8 h) and more delayed recruitment of monocytes (8-24 h) in vivo. A12 (approximately 70 nM) was present in synovial fluid (SF) from rheumatoid arthritis patients, and synovium contained A12-positive neutrophils in the sublining and interstitial region, often surrounding the perivasculature but rarely in the synovial lining layer, although some macrophages were positive. The A12 gene was transiently up-regulated in monocytes by tumor necrosis factor alpha (6 h); induction by lipopolysaccharide (LPS) was sustained (12-48 h). A12 may contribute to leukocyte migration in chronic inflammatory responses.
MeSH terms
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Actins / metabolism
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Animals
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Antigens, Differentiation / metabolism
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Arthritis, Rheumatoid / metabolism
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Arthritis, Rheumatoid / pathology
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Biopolymers / metabolism
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Calcium Signaling / drug effects
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Calcium-Binding Proteins / analysis
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Calcium-Binding Proteins / pharmacology
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Calcium-Binding Proteins / physiology*
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Calgranulin A
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Calgranulin B
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Cells, Cultured / drug effects
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Chemotaxis / drug effects*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation, Leukemic / drug effects
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Humans
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Inflammation / metabolism*
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Leukemia, Monocytic, Acute / pathology
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Lipopolysaccharides / pharmacology
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Lymphocytes / drug effects*
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Macrophages / chemistry
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Macrophages / pathology
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Mice
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Mice, Inbred BALB C
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Monocytes / drug effects*
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Monocytes / metabolism
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neutrophils / chemistry
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Neutrophils / pathology
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RNA, Messenger / biosynthesis
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Rabbits
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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S100 Proteins / metabolism
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S100A12 Protein
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Specific Pathogen-Free Organisms
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Synovial Fluid / chemistry
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Synovial Membrane / pathology
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Actins
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Antigens, Differentiation
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Biopolymers
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Calcium-Binding Proteins
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Calgranulin A
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Calgranulin B
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Lipopolysaccharides
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Neoplasm Proteins
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RNA, Messenger
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Recombinant Proteins
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S100 Proteins
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S100A12 Protein
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S100A12 protein, human
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Tumor Necrosis Factor-alpha