Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-γ production by tumor-associated macrophages
Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-γ production by tumor-associated macrophages
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DOI：
10.1111/j.1349-7006.2009.01296.x
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发表时间：
2009-11-01
期刊：
影响因子：
5.7
通讯作者：
Takeya, Motohiro
中科院分区：
文献类型：
--
作者：
Komohara, Yoshihiro;Takemura, Kenichi;Takeya, Motohiro
A类清道夫受体（SR-A, CD204）在肿瘤相关巨噬细胞（TAM）中高度表达。为了研究SR-A在TAM中的功能，我们给野生型和SR-A缺陷（SR-A-/-）小鼠注射EL4细胞。尽管这两组小鼠在浸润的巨噬细胞和淋巴细胞数量以及新生血管形成方面没有差异，但SR-A-/-小鼠延缓了EL4肿瘤的生长。诱导型一氧化氮（NO）合成酶和干扰素(IFN)- γ mRNA在SR-A-/-小鼠肿瘤组织中的表达显著升高。吞噬坏死的EL4细胞诱导培养的巨噬细胞上调NO和ifn - γ的产生，体外SR-A-/-巨噬细胞中NO和ifn - γ的产生增加。体外培养的SR-A-/-巨噬细胞中ifn - β的产生也升高。这些结果表明，SR-A-/-小鼠巨噬细胞的抗肿瘤活性增加是由于NO和ifn - γ的产生上调。这些数据表明SR-A通过抑制toll样受体（TLR）4- ifn - β信号传导在调节TAM功能中的重要作用。（癌症科学2009）；00: 000 - 000)。
Class A scavenger receptors (SR-A, CD204) are highly expressed in tumor-associated macrophages (TAM). To investigate the function of SR-A in TAM, wild-type and SR-A-deficient (SR-A-/-) mice were injected with EL4 cells. Although these groups of mice did not differ in the numbers of infiltrating macrophages and lymphocytes and in neovascularization, SR-A-/- mice had delayed growth of EL4 tumors. Expression of inducible nitric oxide (NO) synthase and interferon (IFN)-gamma mRNA increased significantly in tumor tissues from SR-A-/- mice. Engulfment of necrotic EL4 cells induced upregulation of NO and IFN-gamma production by cultured macrophages, and production of NO and IFN-gamma increased in SR-A-/- macrophages in vitro. IFN-beta production by cultured macrophages was also elevated in SR-A-/- macrophages in vitro. These results suggested that the antitumor activity of macrophages increased in SR-A-/- mice because of upregulation of NO and IFN-gamma production. These data indicate an important role of SR-A in regulating TAM function by inhibiting toll-like receptor (TLR)4-IFN-beta signaling. (Cancer Sci 2009); 00: 000-000).