ROS play a critical role in the differentiation of alternatively activated macrophages and

ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages

Yan Zhang;Swati Choksi;Kun Chen;Yelena Pobezinskaya;Ilona Linnoila;Zheng-Gang Liu

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2013(023)007

【摘要】Differentiation to different types of macrophages determines their distinct functions.Tumor-associated macrophages (TAMs) promote tumorigenesis owing to their proangiogenic and immune-suppressive functions

similar

to

those

of

alternatively

activated

(M2)

macrophages.We report that reactive oxygen species (ROS) production is critical for macrophage differentiation and that inhibition of superoxide (O2-) production specifically blocks the differentiation of M2 macrophages.We found that when monocytes are triggered to differentiate,O2-is generated and is needed for the biphasic ERK activation,which

is

critical

for

macrophage

differentiation.We

demonstrated that ROS elimination by butylated hydroxyanisole (BHA) and

other

ROS

inhibitors

blocks

macrophage

differentiation.However,the inhibitory effect of ROS elimination on macrophage differentiation is overcome when cells are polarized to classically activated (M1),but not M2,macrophages.More importantly,the continuous administration of the ROS inhibitor BHA efficiently blocked