Imaging of macrophage mitochondria dynamics in vivo reveals cellular activation phenotype for diagnosis
Identifieur interne : 001036 ( Ncbi/Curation ); précédent : 001035; suivant : 001037Imaging of macrophage mitochondria dynamics in vivo reveals cellular activation phenotype for diagnosis
Auteurs : Yue Li [République populaire de Chine] ; Yuan He [République populaire de Chine] ; Kai Miao [République populaire de Chine] ; Ying Zheng [République populaire de Chine] ; Chuxia Deng [République populaire de Chine] ; Tzu-Ming Liu [République populaire de Chine]Source :
- Theranostics [ 1838-7640 ] ; 2020.
Abstract
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
Url:
DOI: 10.7150/thno.40495
PubMed: 32194843
PubMed Central: 7053213
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Imaging of macrophage mitochondria dynamics <italic>in vivo</italic>
reveals cellular activation phenotype for diagnosis</title>
<author><name sortKey="Li, Yue" sort="Li, Yue" uniqKey="Li Y" first="Yue" last="Li">Yue Li</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR</wicri:regionArea>
<wicri:noRegion>Macao SAR</wicri:noRegion>
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<author><name sortKey="He, Yuan" sort="He, Yuan" uniqKey="He Y" first="Yuan" last="He">Yuan He</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR</wicri:regionArea>
<wicri:noRegion>Macao SAR</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Miao, Kai" sort="Miao, Kai" uniqKey="Miao K" first="Kai" last="Miao">Kai Miao</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR</wicri:regionArea>
<wicri:noRegion>Macao SAR</wicri:noRegion>
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<author><name sortKey="Zheng, Ying" sort="Zheng, Ying" uniqKey="Zheng Y" first="Ying" last="Zheng">Ying Zheng</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR</wicri:regionArea>
<wicri:noRegion>Macao SAR</wicri:noRegion>
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<author><name sortKey="Deng, Chuxia" sort="Deng, Chuxia" uniqKey="Deng C" first="Chuxia" last="Deng">Chuxia Deng</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR</wicri:regionArea>
<wicri:noRegion>Macao SAR</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liu, Tzu Ming" sort="Liu, Tzu Ming" uniqKey="Liu T" first="Tzu-Ming" last="Liu">Tzu-Ming Liu</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR</wicri:regionArea>
<wicri:noRegion>Macao SAR</wicri:noRegion>
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<series><title level="j">Theranostics</title>
<idno type="eISSN">1838-7640</idno>
<imprint><date when="2020">2020</date>
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<front><div type="abstract" xml:lang="en"><p>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 <italic>in vivo</italic>
characterization methods to reveal the dynamic activation of macrophages impedes these studies in various disease contexts.</p>
<p><bold>Methods</bold>
: Here,<italic> in vitro</italic>
bone marrow-derived macrophages (BMDMs) and <italic>in vivo</italic>
Matrigel plug were used to evaluate how mitochondria dynamics supports cellular activation and functions. We conducted macrophage repolarization <italic>in vitro</italic>
to track mitochondria dynamics during the shift of activation status. For <italic>in vivo</italic>
diagnosis, a novel MitoTracker-loaded liposome was first developed to label macrophage mitochondria in mice before/after inflammatory stimulation.</p>
<p><bold>Results</bold>
: Based on the typical activation of <italic>in vitro</italic>
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 <italic>in vitro</italic>
, 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<italic> in vivo</italic>
. Their organization dynamics revealed the dynamic change from anti-inflammatory macrophages to inflammatory ones<italic> in vivo</italic>
under the lipopolysaccharide (LPS) challenge.</p>
<p><bold>Conclusion</bold>
: These results reveal that subcellular imaging of mitochondria organization can characterize the activation status of macrophage <italic>in vitro</italic>
and <italic>in vivo</italic>
at a single-cell level, which is critical for the studies of noninvasive diagnosis and therapeutic drug monitoring.</p>
</div>
</front>
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