S100A4 Regulates Macrophage Chemotaxis

Mol Biol Cell. 2010 Aug 1;21(15):2598-610. doi: 10.1091/mbc.e09-07-0609. Epub 2010 Jun 2.

Abstract

S100A4, a member of the S100 family of Ca(2+)-binding proteins, is directly involved in tumor metastasis. In addition to its expression in tumor cells, S100A4 is expressed in normal cells and tissues, including fibroblasts and cells of the immune system. To examine the contribution of S100A4 to normal physiology, we established S100A4-deficient mice by gene targeting. Homozygous S100A4(-/-) mice are fertile, grow normally and exhibit no overt abnormalities; however, the loss of S100A4 results in impaired recruitment of macrophages to sites of inflammation in vivo. Consistent with these observations, primary bone marrow macrophages (BMMs) derived from S100A4(-/-) mice display defects in chemotactic motility in vitro. S100A4(-/-) BMMs form unstable protrusions, overassemble myosin-IIA, and exhibit altered colony-stimulating factor-1 receptor signaling. These studies establish S100A4 as a regulator of physiological macrophage motility and demonstrate that S100A4 mediates macrophage recruitment and chemotaxis in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actomyosin / metabolism
  • Animals
  • Bone Marrow Cells / cytology
  • Cell Count
  • Cell Surface Extensions / drug effects
  • Cell Surface Extensions / metabolism
  • Chemotaxis* / drug effects
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / deficiency
  • S100 Proteins / metabolism*
  • Signal Transduction / drug effects

Substances

  • Heterocyclic Compounds, 4 or More Rings
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • S100a4 protein, mouse
  • blebbistatin
  • Macrophage Colony-Stimulating Factor
  • Actomyosin
  • Receptor, Macrophage Colony-Stimulating Factor