Proinflammatory properties of the human S100 protein S100A12

J Leukoc Biol. 2001 Jun;69(6):986-94.

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.

Publication types

  • Comparative Study

MeSH terms

  • Actins / metabolism
  • Animals
  • Antigens, Differentiation / metabolism
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Biopolymers / metabolism
  • Calcium Signaling / drug effects
  • Calcium-Binding Proteins / analysis
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Calcium-Binding Proteins / pharmacology
  • Calcium-Binding Proteins / physiology*
  • Calgranulin A
  • Calgranulin B
  • Cells, Cultured / drug effects
  • Chemotaxis / drug effects*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Inflammation / metabolism*
  • Leukemia, Monocytic, Acute / pathology
  • Lipopolysaccharides / pharmacology
  • Lymphocytes / drug effects*
  • Macrophages / chemistry
  • Macrophages / pathology
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neutrophils / chemistry
  • Neutrophils / pathology
  • RNA, Messenger / biosynthesis
  • Rabbits
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Proteins / metabolism
  • S100A12 Protein
  • Specific Pathogen-Free Organisms
  • Synovial Fluid / chemistry
  • Synovial Membrane / pathology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Actins
  • Antigens, Differentiation
  • Biopolymers
  • Calcium-Binding Proteins
  • Calgranulin A
  • Calgranulin B
  • Lipopolysaccharides
  • Neoplasm Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • S100 Proteins
  • S100A12 Protein
  • S100A12 protein, human
  • Tumor Necrosis Factor-alpha