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.
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.
Komohara
Yoshihiro
Y
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Japan.
Takemura
Kenichi
K
Lei
Xiao Feng
XF
Sakashita
Naomi
N
Harada
Mamoru
M
Suzuki
Hiroshi
H
Kodama
Tatsuhiko
T
Takeya
Motohiro
M
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
D016207:Cytokines; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; D009569:Nitric Oxide; D007371:Interferon-gamma
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