PMID- 30105024
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20190916
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Notch Signaling Modulates Macrophage Polarization and Phagocytosis Through Direct 
      Suppression of Signal Regulatory Protein alpha Expression.
PG  - 1744
LID - 10.3389/fimmu.2018.01744 [doi]
LID - 1744
AB  - The Notch pathway plays critical roles in the development and functional 
      modulation of myeloid cells. Previous studies have demonstrated that Notch 
      activation promotes M1 polarization and phagocytosis of macrophages; however, the 
      downstream molecular mechanisms mediating Notch signal remain elusive. In an 
      attempt to identify Notch downstream targets in bone marrow-derived macrophages 
      (BMDMs) using mass spectrometry, the signal regulatory protein alpha (SIRPalpha) appeared 
      to respond to knockout of recombination signal-binding protein Jk (RBP-J), the 
      critical transcription factor of Notch pathway, in macrophages. In this study, we 
      validated that Notch activation could repress SIRPalpha expression likely via the Hes 
      family co-repressors. SIRPalpha promoted macrophage M2 polarization, which was 
      dependent on the interaction with CD47 and mediated by intracellular signaling 
      through SHP-1. We provided evidence that Notch signal regulated macrophage 
      polarization at least partially through SIRPalpha. Interestingly, Notch signal 
      regulated macrophage phagocytosis of tumor cells through SIRPalpha but in a 
      SHP-1-independent way. To access the translational value of our findings, we 
      expressed the extracellular domains of the mouse SIRPalpha (mSIRPalpha(ext)) to block the 
      interaction between CD47 and SIRPalpha. We demonstrated that the soluble mSIRPalpha(ext) 
      polypeptides could promote M1 polarization and increase phagocytosis of tumor 
      cells by macrophages. Taken together, our results provided new insights into the 
      molecular mechanisms of notch-mediated macrophage polarization and further 
      validated SIRPalpha as a target for tumor therapy through modulating macrophage 
      polarization and phagocytosis.
FAU - Lin, Yan
AU  - Lin Y
AD  - Department of Pediatrics, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, China.
AD  - Department of Hematology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, China.
AD  - Department of Genetics and Developmental Biology, Fourth Military Medical 
      University, Xi'an, China.
FAU - Zhao, Jun-Long
AU  - Zhao JL
AD  - Department of Genetics and Developmental Biology, Fourth Military Medical 
      University, Xi'an, China.
AD  - Department of Biochemistry and Molecular Biology, Fourth Military Medical 
      University, Xi'an, China.
FAU - Zheng, Qi-Jun
AU  - Zheng QJ
AD  - Department of Cardiac Surgery, Xijng Hospital, Fourth Military Medical 
      University, Xi'an, China.
FAU - Jiang, Xun
AU  - Jiang X
AD  - Department of Pediatrics, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Tian, Jiao
AU  - Tian J
AD  - Department of Pediatrics, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Liang, Shi-Qian
AU  - Liang SQ
AD  - Department of Genetics and Developmental Biology, Fourth Military Medical 
      University, Xi'an, China.
FAU - Guo, Hong-Wei
AU  - Guo HW
AD  - Department of Pediatrics, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Qin, Hong-Yan
AU  - Qin HY
AD  - Department of Genetics and Developmental Biology, Fourth Military Medical 
      University, Xi'an, China.
FAU - Liang, Ying-Min
AU  - Liang YM
AD  - Department of Hematology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Han, Hua
AU  - Han H
AD  - Department of Genetics and Developmental Biology, Fourth Military Medical 
      University, Xi'an, China.
AD  - Department of Biochemistry and Molecular Biology, Fourth Military Medical 
      University, Xi'an, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180730
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (CD47 Antigen)
RN  - 0 (CD47 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Ptpns1 protein, mouse)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Animals
MH  - CD47 Antigen/metabolism
MH  - Carrier Proteins
MH  - Cell Line, Tumor
MH  - *Gene Expression Regulation
MH  - Immunomodulation
MH  - Macrophage Activation/*immunology
MH  - Macrophages/*immunology/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - *Phagocytosis
MH  - Phosphorylation
MH  - Protein Binding
MH  - Receptors, Immunologic/*genetics/metabolism
MH  - Receptors, Notch/*metabolism
PMC - PMC6077186
OTO - NOTNLM
OT  - SHP-1
OT  - macrophages
OT  - notch
OT  - phagocytosis
OT  - polarization
OT  - signal regulatory protein alpha
EDAT- 2018/08/15 06:00
MHDA- 2019/09/17 06:00
PMCR- 2018/01/01
CRDT- 2018/08/15 06:00
PHST- 2018/03/24 00:00 [received]
PHST- 2018/07/16 00:00 [accepted]
PHST- 2018/08/15 06:00 [entrez]
PHST- 2018/08/15 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.01744 [doi]
PST - epublish
SO  - Front Immunol. 2018 Jul 30;9:1744. doi: 10.3389/fimmu.2018.01744. eCollection 
      2018.