Transgenic expression of CSF-1 in CSF-1 receptor-expressing cells leads to macrophage activation, osteoporosis, and early death

Suwen Wei, Xu Ming Dai, E. Richard Stanley

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

CSF-1 is the primary mononuclear phagocyte and osteoclast growth factor. Autocrine regulation by CSF-1 has been reported in macrophages during inflammatory responses and in neoplastic cells. To investigate whether inflammatory disease or neoplasia was the dominant consequence of autocrine regulation by CSF-1 in CSF-1 receptor (CSF-1R)-expressing cells, we created mice that express CSF-1 under the control of the CSF-1R promoter/first intron driver [transgene TgN(Csf1r-Csf1)Ers (TgRC) mice], which have reduced thymic size, a short lifetime, and low body weight and develop osteoporosis. In 4-week-old TgRC mice, osteoclast numbers are elevated, and macrophage densities are increased in bone marrow, spleen, liver, and brain. Cultured TgRC macrophages express CSF-1 and proliferate without exogenous CSF-1 and in the presence of neutralizing antimouse CSF-1 antibody. Compared with macrophages from nontransgenic littermates, TgRC macrophages exhibit a stellate morphology, express elevated mRNAs for proinflammatory cytokines, and despite a lower, steady-state cytokine secretion, secrete elevated levels of inflammatory cytokines in response to LPS, indicating that TgRC macrophages are functionally primed through the CSF-1R. Thus, autocrine regulation of CSF-1R-expressing cells by CSF-1 leads to a severe phenotype that emphasizes the importance of the known, local production of CSF-1 in inflammatory disease.

Original languageEnglish (US)
Pages (from-to)1445-1453
Number of pages9
JournalJournal of Leukocyte Biology
Volume80
Issue number6
DOIs
Publication statusPublished - Dec 1 2006

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Keywords

  • Autocrine regulation
  • Cytokine
  • Inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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