RT Journal Article
SR Electronic
T1 G-CSF shifts erythropoiesis from bone marrow into spleen in the setting of systemic inflammation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000737
DO 10.26508/lsa.202000737
VO 4
IS 1
A1 Weiqiang Jing
A1 Xing Guo
A1 Fei Qin
A1 Yue Li
A1 Ganyu Wang
A1 Yuxuan Bi
A1 Xing Jin
A1 Lihui Han
A1 Xiaoyuan Dong
A1 Yunxue Zhao
YR 2021
UL https://www.life-science-alliance.org/content/4/1/e202000737.abstract
AB The anemia of inflammation is related in part to abnormal erythropoiesis in bone marrow. G-CSF regulates granulopoiesis and is increased during systemic inflammation. Here, we have showed that high levels of G-CSF are associated with repression of bone marrow erythropoiesis and expansion of splenic erythropoiesis in Escherichia coli–infected mice and lipopolysaccharide-treated mice. Under lipopolysaccharide-induced systemic inflammatory conditions in mice, G-CSF neutralization with antibody alleviated the blockage of bone marrow erythropoiesis, prevented the enhancement of splenic erythropoiesis, ameliorated splenomegaly, and reduced the brittleness of spleen. We further demonstrated that after lipopolysaccharide treatment, TLR4-knockout mice display low levels of G-CSF, healthy bone marrow erythropoiesis, almost no stress erythropoiesis in the spleen, and normal size and toughness of spleen. In addition, we found HIF-mediated erythropoietin production is essential for splenic erythropoiesis in the setting of G-CSF-induced suppression of bone marrow erythropoiesis. Our findings identify G-CSF as a critical mediator of inflammation-associated erythropoiesis dysfunction in bone marrow and offer insight into the mechanism of G-CSF-induced splenic erythropoiesis. We provide experimentally significant dimension to the biology of G-CSF.