title: Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-gamma production by tumor-associated macrophages.
abstract: 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.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takemura
authors.forename: Xiao Feng
authors.initials: XF
authors.lastname: Lei
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
authors.forename: Mamoru
authors.initials: M
authors.lastname: Harada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis*; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D051117:Scavenger Receptors, Class A / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; D009569:Nitric Oxide; D007371:Interferon-gamma
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