PMID- 32194843
OWN - NLM
STAT- MEDLINE
DCOM- 20210330
LR  - 20210330
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 10
IP  - 7
DP  - 2020
TI  - Imaging of macrophage mitochondria dynamics in vivo reveals cellular activation 
      phenotype for diagnosis.
PG  - 2897-2917
LID - 10.7150/thno.40495 [doi]
AB  - Highly plastic macrophages are pivotal players in the body's homeostasis and 
      pathogenesis. Grasping the molecular or cellular factors that drive and support 
      the macrophage activation will help to develop diagnostics and manipulate their 
      functions in these contexts. However, the lack of in vivo characterization 
      methods to reveal the dynamic activation of macrophages impedes these studies in 
      various disease contexts. Methods: Here, in vitro bone marrow-derived macrophages 
      (BMDMs) and in vivo Matrigel plug were used to evaluate how mitochondria dynamics 
      supports cellular activation and functions. We conducted macrophage 
      repolarization in vitro to track mitochondria dynamics during the shift of 
      activation status. For in vivo diagnosis, a novel MitoTracker-loaded liposome was 
      first developed to label macrophage mitochondria in mice before/after 
      inflammatory stimulation. Results: Based on the typical activation of in vitro 
      BMDMs, we found glycolysis based macrophages have punctate and discrete 
      mitochondria, while OXPHOS active macrophages have elongated and interconnected 
      mitochondria. M1, M2a, M2b, and M2c activated BMDMs showed clustered and 
      differentiable features in mitochondrial morphology. These features also hold for 
      Matrigel plug-recruited macrophages in mice. Furthermore, with the interventions 
      on M2a macrophages in vitro, we demonstrated that mitochondria morphology could 
      be a metabolic index to evaluate macrophage activation status under drug 
      manipulation. Using the MitoTracker-loaded liposomes, we further achieved 
      subcellular imaging of macrophage mitochondria in vivo. Their organization 
      dynamics revealed the dynamic change from anti-inflammatory macrophages to 
      inflammatory ones in vivo under the lipopolysaccharide (LPS) challenge. 
      Conclusion: These results reveal that subcellular imaging of mitochondria 
      organization can characterize the activation status of macrophage in vitro and in 
      vivo at a single-cell level, which is critical for the studies of noninvasive 
      diagnosis and therapeutic drug monitoring.
CI  - (c) The author(s).
FAU - Li, Yue
AU  - Li Y
AD  - Institute of Translational Medicine, Faculty of Health Sciences, University of 
      Macau, Taipa, Macao SAR, China.
FAU - He, Yuan
AU  - He Y
AD  - Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, 
      China.
FAU - Miao, Kai
AU  - Miao K
AD  - Institute of Translational Medicine, Faculty of Health Sciences, University of 
      Macau, Taipa, Macao SAR, China.
FAU - Zheng, Ying
AU  - Zheng Y
AD  - Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, 
      China.
FAU - Deng, Chuxia
AU  - Deng C
AD  - Institute of Translational Medicine, Faculty of Health Sciences, University of 
      Macau, Taipa, Macao SAR, China.
FAU - Liu, Tzu-Ming
AU  - Liu TM
AD  - Institute of Translational Medicine, Faculty of Health Sciences, University of 
      Macau, Taipa, Macao SAR, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200203
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Biomarkers)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cells, Cultured
MH  - *Macrophage Activation
MH  - *Macrophages/metabolism/ultrastructure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - *Mitochondria/metabolism/ultrastructure
MH  - Single-Cell Analysis/*methods
PMC - PMC7053213
OTO - NOTNLM
OT  - in vivo imaging
OT  - liposome
OT  - macrophage
OT  - mitochondria
OT  - multiphoton microscopy
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/03/21 06:00
MHDA- 2021/03/31 06:00
PMCR- 2020/01/01
CRDT- 2020/03/21 06:00
PHST- 2019/09/21 00:00 [received]
PHST- 2020/01/14 00:00 [accepted]
PHST- 2020/03/21 06:00 [entrez]
PHST- 2020/03/21 06:00 [pubmed]
PHST- 2021/03/31 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - thnov10p2897 [pii]
AID - 10.7150/thno.40495 [doi]
PST - epublish
SO  - Theranostics. 2020 Feb 3;10(7):2897-2917. doi: 10.7150/thno.40495. eCollection 
      2020.