PMID- 36998073
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230403
IS  - 2045-3701 (Print)
IS  - 2045-3701 (Electronic)
IS  - 2045-3701 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Mar 30
TI  - N-methyl-D-aspartate receptors induce M1 polarization of macrophages: Feasibility 
      of targeted imaging in inflammatory response in vivo.
PG  - 69
LID - 10.1186/s13578-023-01007-5 [doi]
LID - 69
AB  - BACKGROUND: N-methyl-D-aspartate receptors (NMDARs) are considered to be involved 
      in several physiological and pathophysiological processes in addition to the 
      progression of neurological disorders. However, how NMDARs are involved in the 
      glycolytic phenotype of M1 macrophage polarization and the possibility of using 
      them as a bio-imaging probe for macrophage-mediated inflammation remain unclear. 
      METHODS: We analyzed cellular responses to NMDAR antagonism and small interfering 
      RNAs using mouse bone marrow-derived macrophages (BMDMs) treated with 
      lipopolysaccharide (LPS). An NMDAR targeting imaging probe, N-TIP, was produced 
      via the introduction of NMDAR antibody and the infrared fluorescent dye FSD 
      Fluor 647. N-TIP binding efficiency was tested in intact and LPS-stimulated 
      BMDMs. N-TIP was intravenously administered to mice with carrageenan (CG)- and 
      LPS-induced paw edema, and in vivo fluorescence imaging was conducted. The 
      anti-inflammatory effects of dexamethasone were evaluated using the 
      N-TIP-mediated macrophage imaging technique. RESULTS: NMDARs were overexpressed 
      in LPS-treated macrophages, subsequently inducing M1 macrophage polarization. 
      Mechanistically, NMDAR-mediated Ca(2+) accumulation resulted in LPS-stimulated 
      glycolysis via upregulation of PI3K/AKT/mTORC1 signaling. In vivo fluorescence 
      imaging with N-TIP showed LPS- and CG-induced inflamed lesions at 5 h 
      post-inflammation, and the inflamed lesions could be detected until 24 h. 
      Furthermore, our N-TIP-mediated macrophage imaging technique helped successfully 
      visualize the anti-inflammatory effects of dexamethasone in mice with 
      inflammation. CONCLUSION: This study demonstrates that NMDAR-mediated glycolysis 
      plays a critical role in M1 macrophage-related inflammation. Moreover, our 
      results suggest that NMDAR targeting imaging probe may be useful in research on 
      inflammatory response in vivo.
CI  - (c) 2023. The Author(s).
FAU - Jeon, Hui-Jeon
AU  - Jeon HJ
AD  - New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation 
      (KMEDIhub), 80 Chembok-Ro, Daegu, 41061, South Korea.
FAU - Byun, Jun-Kyu
AU  - Byun JK
AD  - BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, 
      Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook 
      National University, Daegu, 41566, South Korea.
FAU - Lee, Sang Bong
AU  - Lee SB
AD  - THERABEST, Co., Ltd, 06657, Seoul, South Korea.
FAU - Son, Kwang Hee
AU  - Son KH
AD  - Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation 
      (KMEDIhub), 41061, Daegu, South Korea.
FAU - Lim, Ji-Youn
AU  - Lim JY
AD  - New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation 
      (KMEDIhub), 80 Chembok-Ro, Daegu, 41061, South Korea.
FAU - Lee, Da Sol
AU  - Lee DS
AD  - Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation 
      (KMEDIhub), 41061, Daegu, South Korea.
FAU - Kim, Kil Soo
AU  - Kim KS
AD  - Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation 
      (KMEDIhub), 41061, Daegu, South Korea.
AD  - College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, 
      South Korea.
FAU - Park, Jin Woo
AU  - Park JW
AD  - BioActs.Co., Ltd., 21666, Incheon, South Korea.
FAU - Shin, Gyeong Rim
AU  - Shin GR
AD  - BioActs.Co., Ltd., 21666, Incheon, South Korea.
FAU - Kim, Ye Jin
AU  - Kim YJ
AD  - Department of Internal Medicine, School of Medicine, Kyungpook National 
      University, Kyungpook National University Hospital, Daegu, 41944, South Korea.
AD  - Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, 
      41566, South Korea.
FAU - Jin, Jonghwa
AU  - Jin J
AD  - Department of Internal Medicine, School of Medicine, Kyungpook National 
      University, Kyungpook National University Hospital, Daegu, 41944, South Korea.
FAU - Kim, Daehoon
AU  - Kim D
AD  - Department of Biomedical Science, Kyungpook National University, Daegu, 41566, 
      South Korea.
FAU - Kim, Dong-Ho
AU  - Kim DH
AD  - Department of Biomedical Science, Kyungpook National University, Daegu, 41566, 
      South Korea.
FAU - Yu, Ji Hoon
AU  - Yu JH
AD  - New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation 
      (KMEDIhub), 80 Chembok-Ro, Daegu, 41061, South Korea.
FAU - Choi, Yeon-Kyung
AU  - Choi YK
AD  - Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, 
      41566, South Korea. ykchoi@knu.ac.kr.
AD  - Department of Internal Medicine, School of Medicine, Kyungpook National 
      University, Kyungpook National University Chilgok Hospital, Daegu, 41404, South 
      Korea. ykchoi@knu.ac.kr.
FAU - Park, Keun-Gyu
AU  - Park KG
AD  - Department of Internal Medicine, School of Medicine, Kyungpook National 
      University, Kyungpook National University Hospital, Daegu, 41944, South Korea. 
      kpark@knu.ac.kr.
AD  - Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, 
      41566, South Korea. kpark@knu.ac.kr.
AD  - Department of Biomedical Science, Kyungpook National University, Daegu, 41566, 
      South Korea. kpark@knu.ac.kr.
FAU - Jeon, Yong Hyun
AU  - Jeon YH
AD  - Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation 
      (KMEDIhub), 41061, Daegu, South Korea. jeon9014@dgmif.re.kr.
AD  - Leading-Edge Research Center for Drug Discovery and Development for Diabetes and 
      Metabolic Disease, Kyungpook National University Hospital, Daegu, 41404, South 
      Korea. jeon9014@dgmif.re.kr.
LA  - eng
GR  - 2017R1D1A1B03028340/National Research Foundation of Korea/
GR  - 2019R1F1A1057906/National Research Foundation of Korea/
GR  - 2020R1A5A2017323/National Research Foundation of Korea/
GR  - 2021R1C1C2003405/National Research Foundation of Korea/
GR  - 2021R1A2C3005603/Korea National Sport University/
GR  - HI16C1501/Ministry of Health and Welfare/
GR  - HI15C0001/Ministry of Health and Welfare/
GR  - HI19C0760/Ministry of Health and Welfare/
GR  - 2022R1A2C100859111/National research foundation of korea/
PT  - Journal Article
DEP - 20230330
PL  - England
TA  - Cell Biosci
JT  - Cell & bioscience
JID - 101561195
PMC - PMC10064586
OTO - NOTNLM
OT  - Antibody-mediated imaging
OT  - Inflammation
OT  - Macrophage
OT  - N-methyl-D-aspartate receptors
OT  - Near-infrared fluorescent
COIS- The authors declare no competing interests.
EDAT- 2023/03/31 06:00
MHDA- 2023/03/31 06:01
PMCR- 2023/03/30
CRDT- 2023/03/30 23:43
PHST- 2022/05/18 00:00 [received]
PHST- 2023/03/06 00:00 [accepted]
PHST- 2023/03/31 06:01 [medline]
PHST- 2023/03/30 23:43 [entrez]
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/30 00:00 [pmc-release]
AID - 10.1186/s13578-023-01007-5 [pii]
AID - 1007 [pii]
AID - 10.1186/s13578-023-01007-5 [doi]
PST - epublish
SO  - Cell Biosci. 2023 Mar 30;13(1):69. doi: 10.1186/s13578-023-01007-5.