Visualizing inflammation with an M1 macrophage selective probe via GLUT1 as the gating target

Cho, Heewon; Kwon, Hyeokjin; Sharma, Amit; Lee, Sun Hyeok; Liu, Xiao; Miyamoto, Naoki; Kim, Jong-Jin; Im, Sin Hyeog; Kang, Nam‐Young; Chang, Young‐Tae

doi:10.1038/s41467-022-33526-z

Cited by 37 publications

(26 citation statements)

References 33 publications

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“…Mouse bone marrow-derived macrophages (BMDMs) were treated with lipopolysaccharide (LPS) and interferon gamma (IFNg) to induce M1 polarization, and IL-4 to induce M2 polarization, and expression of facilitative (GLUT) and sodium dependent (SGLT) glucose transporters isoforms were assessed by quantitative real-time RT-PCR (qRT-PCR). Consistent with previous studies, GLUT1 mRNA expression was elevated in M1 macrophages (Cho et al, 2022;Freemerman et al, 2019).…”

Section: Glut3 Is Induced By M2 Stimuli and Required For M2 Polarizat...supporting

confidence: 92%

Endosomal GLUT3 is essential for alternative macrophage signaling, polarization, and function

Lee

Rose

et al. 2022

Preprint

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Macrophages play critical roles in both inflammation and tissue homeostasis. Classically activated (M1) macrophages promote antimicrobial and tumoricidal activity, while alternatively activated (M2) macrophages promote phagocytosis and tissue homeostasis. The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in different hematopoietic lineages, but their specific functions in macrophages is poorly understood. We discovered that GLUT3 expression was increased after M2-activation stimuli in macrophages. Notably, GLUT3 KO BMDM (bone marrow-derived macrophages) showed marked defects in M2, but not M1, polarization. Consistent with defects in M2 polarization, GLUT3 KO macrophages showed impaired wound healing and decreased inflammation in calcipotriol-induced, atopic dermatitis-like inflammation. GLUT3 promoted IL-4/STAT6 signaling, the main signaling pathway for M2 polarization, in a glucose-transport independent manner. Unlike plasma membrane-localized GLUT1, GLUT3 and components of the IL-4 signaling pathway, localized primarily to endosomes. GLUT3, but not GLUT1, interacted with Ras through its intracytoplasmic loop, and Rac1-PAK-cofilin signaling and the endocytosis of IL4R subunits were impaired in the absence of GLUT3. Thus, GLUT3 is essential for alternative macrophage polarization and function and plays an unexpected role in the regulation of endosomal signaling.

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Section: Glut3 Is Induced By M2 Stimuli and Required For M2 Polarizat...supporting

confidence: 92%

Endosomal GLUT3 is essential for alternative macrophage signaling, polarization, and function

Lee

Rose

et al. 2022

Preprint

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“…These findings broaden the mechanistic view with a facilitated target identification process on the one hand and further motivate the design of a focused-fluorescent library. Our group verified the usefulness of the strategy through M1 selective probe CDr17 development by utilizing the preferred carbohydrate uptake character of M1 cells through the luminescent-carbohydrate library …”

Section: Introductionmentioning

confidence: 79%

“…Our group verified the usefulness of the strategy through M1 selective probe CDr17 development by utilizing the preferred carbohydrate uptake character of M1 cells through the luminescent-carbohydrate library. 5 In this study, for M2 selective probe development, we paid attention to the enhanced FA uptake of M2 cells and established a luminescent-FA library. After the unbiased screening, we elucidated a unique M2 selective probe CDg18 and explicated its staining mechanism through GOLD, using a specifically overexpressed FA transporter in of the repolarization of M2 toward M1 by a small-molecule effector.…”

Section: ■ Introductionmentioning

confidence: 99%

Development of a Fluorescent Probe for M2 Macrophages via Gating-Oriented Live-Cell Distinction

et al. 2023

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Macrophages are the most plastic immune cells by changing their characters in response to environmental stimuli. Broadly, macrophages are categorized into two different subsets based on M1/M2 paradigm, which exhibit completely contrary phenotypes. Whereas M1 macrophages are aggressive to offend invaders such as bacteria and tumors, M2 are anti-inflammatory cells and seemingly help tumor immunity. Tumor-associated macrophages are typical examples of M2 cells as the key components of forming and maintaining the tumor microenvironment. Despite the intensive interest, monitoring M2 macrophages in real time is hampered by the lack of competent detection tools. Here, we report the first M2 selective probe CDg18 with a novel mechanism of gating-oriented live-cell distinction through M2-favored fatty acid transporters. To demonstrate the potential of CDg18, we visualize the progressive phenotypic change of M2 toward M1 using a resveratrol analogue HS-1793 as a reprogramming effector. Combined together with M1 probe CDr17, the diminishing M2 character and emerging M1 markers could be simultaneously monitored in real time through the multicolor changes during macrophage reprogramming.

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“…However, differentiating macrophages (M1 and M2) is mainly based on different biomarkers like the cytokine expressed in the two different phenotypes of macrophages. − This involves immunohistochemistry, which is tedious and expensive. As an alternative, small molecular fluorescent probes − are promising diagnostic tools due to their simplicity, cost-effectiveness, and high sensitivity with good resolution.…”

Section: Introductionmentioning

confidence: 99%

A Photoinduced Electron Transfer-Based Hypochlorite-Specific Fluorescent Probe for Selective Imaging of Proinflammatory M1 in a Rheumatoid Arthritis Model

et al. 2023

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The differentiation of the distinct phenotypes of macrophages is essential for monitoring the stage of inflammatory diseases for accurate diagnosis and treatment. Recent studies revealed that the level of hypochlorite (OCl–) varies from activated M1 macrophages (killing pathogens) to M2 (resolution of inflammation) during inflammation. Thus, we developed a simple and efficient fluorescent probe for discriminating M1 from M0 and M2. Herein, fluorescent-based imaging is applied as an alternative to immunohistochemistry, which is challenging due to the tedious process and high cost. We developed a hypochlorite-specific probe PMS-T to differentiate M1 and M2, employing a metabolism-oriented live-cell distinction. This probe enables the detection of inflammatory rheumatoid arthritis in an ex vivo mouse model. Thus, it can be a potential chemical tool for monitoring inflammatory diseases, including rheumatoid arthritis, that may overcome the existing barriers of immunohistochemistry.

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Visualizing inflammation with an M1 macrophage selective probe via GLUT1 as the gating target

Cited by 37 publications

References 33 publications

Endosomal GLUT3 is essential for alternative macrophage signaling, polarization, and function

Endosomal GLUT3 is essential for alternative macrophage signaling, polarization, and function

Development of a Fluorescent Probe for M2 Macrophages via Gating-Oriented Live-Cell Distinction

A Photoinduced Electron Transfer-Based Hypochlorite-Specific Fluorescent Probe for Selective Imaging of Proinflammatory M1 in a Rheumatoid Arthritis Model

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