TY - JOUR
T1 - S100A4 regulates macrophage chemotaxis
AU - Li, Zhong Hua
AU - Dulyaninova, Natalya G.
AU - House, Reniqua P.
AU - Almo, Steven C.
AU - Bresnick, Anne R.
PY - 2010/8/1
Y1 - 2010/8/1
N2 - S100A4, a member of the S100 family of Ca2+-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.
AB - S100A4, a member of the S100 family of Ca2+-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.
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U2 - 10.1091/mbc.E09-07-0609
DO - 10.1091/mbc.E09-07-0609
M3 - Article
C2 - 20519440
AN - SCOPUS:77955115945
SN - 1059-1524
VL - 21
SP - 2598
EP - 2610
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 15
ER -