Transgenic expression of CSF‐1 in CSF‐1 receptor‐expressing cells leads to macrophage activation, osteoporosis, and early death
Transgenic expression of CSF‐1 in CSF‐1 receptor‐expressing cells leads to macrophage activation, osteoporosis, and early death
复制标题
DOI：
10.1189/jlb.0506304
复制
发表时间：
2006-12
影响因子：
5.5
通讯作者：
Suwen Wei;Xu-ming Dai;E. Stanley
中科院分区：
文献类型：
--
作者：
Suwen Wei;Xu-ming Dai;E. Stanley
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.
