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Visualizing Macrophage Phenotypes and Polarization in Diseases: From Biomarkers to Molecular Probes

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Abstract

Macrophage is a kind of immune cell and performs multiple functions including pathogen phagocytosis, antigen presentation and tissue remodeling. To fulfill their functionally distinct roles, macrophages undergo polarization towards a spectrum of phenotypes, particularly the classically activated (M1) and alternatively activated (M2) subtypes. However, the binary M1/M2 phenotype fails to capture the complexity of macrophages subpopulations in vivo. Hence, it is crucial to employ spatiotemporal imaging techniques to visualize macrophage phenotypes and polarization, enabling the monitoring of disease progression and assessment of therapeutic responses to drug candidates. This review begins by discussing the origin, function and diversity of macrophage under physiological and pathological conditions. Subsequently, we summarize the identified macrophage phenotypes and their specific biomarkers. In addition, we present the imaging probes locating the lesions by visualizing macrophages with specific phenotype in vivo. Finally, we discuss the challenges and prospects associated with monitoring immune microenvironment and disease progression through imaging of macrophage phenotypes.

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Abbreviations

AS:

Atherosclerosis

BNIP3:

Adenovirus E1B 19-kDa-interacting protein 3

CD163:

Hemoglobin–haptoglobin scavenger receptor

CD206:

Mannose receptor

COX-2 :

Cyclooxygenase-2

CSF1R:

Colony-stimulating factor receptor

CXCL4:

Chemokine (C-X-C motif) Ligand 4

DN-ICG:

Dextran–indocyanine green

FAD:

Flavin adenine dinucleotide

FR-β:

Folate receptor-β

FUNDC1:

FUN14 domain-containing protein 1

GLUTs:

Glucose transporters

HFHC:

High-fat and high-cholesterol diet

HIF1α:

Hypoxia-induced factor 1α

iNOS:

Nitric oxide synthase

IFN:

Interferon

IL :

Interleukin

LDs:

Lipid droplets

LPS:

Lipopolysaccharide

M1:

Pro-inflammatory macrophage

M2:

Anti-inflammatory macrophage

MARCO:

Macrophage receptor with collagenous structure

M-CSF:

Macrophage Colony Stimulating Factor 1

MHC-II:

Major histocompatibility complex II

MMP7:

Metalloproteinase-7

MRI:

Magnetic resonance imaging

NAFL:

Non-alcoholic fatty liver

NF-κB:

Nuclear factor kappa-light-chain enhancer of B cell

NIR-II:

Second near-infrared window

OCT-NIRF:

Optical coherence tomography–near-infrared fluorescence

OI:

Optical imaging

OXPHOS:

Oxidative phosphorylation

PET:

Positron emission tomography

PINK1:

PTEN Induced Putative Kinase 1

PPARγ:

Peroxisome proliferator-activated receptor gamma

RA:

Rheumatoid arthritis

ROS:

Reactive oxygen species

S100A8:

Calgranulin-A

SIGN-R1:

Specific ICAM-3-grabbing nonintegrin-related 1 receptors

SPECT/CT:

Single-photon emission computed tomography/computed tomography

STAT6:

Signal transducer and activator of transcription 6

TAMs:

Tumor-associated macrophages

TB:

Tumor-bearing

TCA:

Tricarboxylic acid cycle

TLRs:

Toll-like receptors

TNF:

Tumor necrosis factor

TSPO:

18 KDa translocator protein

VEGFA:

Vascular endothelial growth factor A

WT:

Wildtype

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 92159304, 82227806), the National Science Fund for Distinguished Young Scholars (No. 82025019), and the Shanghai Municipal Health Commission Project (202040106).

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DN and HZ contributed equally to this work. DN and HZ performed the literature survey and wrote the manuscript. PW participated in manuscript revision work. FX participated in the final manuscript version. CL provided the theme and corrected the manuscript.

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Correspondence to Cong Li.

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Ni, D., Zhou, H., Wang, P. et al. Visualizing Macrophage Phenotypes and Polarization in Diseases: From Biomarkers to Molecular Probes. Phenomics 3, 613–638 (2023). https://doi.org/10.1007/s43657-023-00129-7

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  • DOI: https://doi.org/10.1007/s43657-023-00129-7

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