S100A4 regulates macrophage chemotaxis.

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.

journal_name

Mol Biol Cell

authors

Li ZH,Dulyaninova NG,House RP,Almo SC,Bresnick AR

doi

10.1091/mbc.e09-07-0609

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

2598-610

issue

15

eissn

1059-1524

issn

1939-4586

pii

E09-07-0609

journal_volume

21

pub_type

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