Depletion and Reconstitution of Macrophages in Mice

Weisser, Shelley B.; Rooijen, Nico van; Sly, Laura M.

doi:10.3791/4105-v

Cited by 5 publications

(8 citation statements)

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“…To demonstrate the contribution of macrophages to hernia regression, they were systemically depleted via intravenous administration of commercially available liposomes loaded with clodronate (dichloromethylene-bisphosphonate, Liposoma), a drug that selectively induces apoptosis of macrophages upon phagocytosis 15 , 16 . Macrophage depletion is expected to occur at around 24 h after intravenous administration, and circulating monocyte depletion is reported to peak at 18 h after administration 17 .…”

Section: Resultsmentioning

confidence: 99%

“…Macrophage depletion is expected to occur at around 24 h after intravenous administration, and circulating monocyte depletion is reported to peak at 18 h after administration 17 . However, repopulating monocytes can be recruited from the bone marrow within a relatively short time, so repeated administrations were performed for a more prolonged macrophage and monocyte depletion 16 , 18 . Two transiently depleted groups were analyzed to understand the macrophage contribution along the progression of hernia formation and regression.…”

Section: Resultsmentioning

confidence: 99%

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Macrophage-based therapy for intervertebral disc herniation: preclinical proof-of-concept

et al. 2023

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Intervertebral disc (IVD) degeneration and herniation is a leading cause of disability globally and a large unmet clinical need. No efficient non-surgical therapy is available, and there is an urgency for minimally invasive therapies capable of restoring tissue function. IVD spontaneous hernia regression following conservative treatment is a clinically relevant phenomenon that has been linked to an inflammatory response. This study establishes the central role of macrophages in IVD spontaneous hernia regression and provides the first preclinical demonstration of a macrophage-based therapy for IVD herniation. A rat model of IVD herniation was used to test complementary experimental setups: (1) macrophage systemic depletion via intravenous administration of clodronate liposomes (Group CLP2w: depletion between 0 and 2 weeks post-lesion; Group CLP6w: depletion between 2 and 6 weeks post-lesion), and (2) administration of bone marrow-derived macrophages into the herniated IVD, 2 weeks post-lesion (Group Mac6w). Herniated animals without treatment were used as controls. The herniated area was quantified by histology in consecutive proteoglycan/collagen IVD sections at 2 and 6 weeks post-lesion. Clodronate-mediated macrophage systemic depletion was confirmed by flow cytometry and resulted in increased hernia sizes. Bone marrow-derived macrophages were successfully administered into rat IVD hernias resulting in a 44% decrease in hernia size. No relevant systemic immune reaction was identified by flow cytometry, cytokine, or proteomic analysis. Furthermore, a possible mechanism for macrophage-induced hernia regression and tissue repair was unveiled through IL4, IL17a, IL18, LIX, and RANTES increase. This study represents the first preclinical proof-of-concept of macrophage-based immunotherapy for IVD herniation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Macrophage-based therapy for intervertebral disc herniation: preclinical proof-of-concept

et al. 2023

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“…5 mg/ml clodronate-liposome were produced for macrophage depletion. The in vivo macrophage depletion was performed as previous description with minor modification (Weisser et al, 2012). Briefly, clodronate or PBS liposomes (200 ll) were i.p.…”

Section: Macrophage Depletion In Vivomentioning

confidence: 99%

Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation

Wu,

Ge,

Wang

et al. 2023

EMBO Mol Med

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Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage‐mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3‐associated phagocytosis (LAP), a non‐canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G‐protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL‐induced efferocytosis, anti‐colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3‐associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.

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“…To investigate the effect of choroidal-resident macrophages on myopia in a mouse model, 3-weeks-old C57BL/6 J mice were randomly divided into 2 groups and were injected intraperitoneally with clodronate or phosphate-buffered saline (PBS) liposomes. In the clodronate liposome group, after being engulfed by macrophages, the clodronate liposomes were degraded by lysosomal phospholipases, which released clodronate into the macrophages and induced apoptosis, thereby promoting macrophage depletion (40). The injection volume of clodronate liposome was 0.1 ml per 10 g of mice and the injection frequency was once every two days.…”

Section: Sustained Intraperitoneal Injection Of Clodronate Liposome D...mentioning

confidence: 99%

The orientation of choroidal macrophage polarization significantly influences the development of myopia in murine models

Hou

Ikeda

Mori

et al. 2023

Preprint

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Myopia is a primary contributor to visual impairment and has emerged as a global public health concern. Evidence indicates that one of the main structural features of myopia is the corresponding decrease in choroidal thickness, and choroidal macrophages play an important role in maintaining the choroidal thickness. Nevertheless, the effect of choroidal macrophages on myopia remains unclear. Here, we discovered that the continuous intraperitoneal injection of clodronate liposomes depleted choroidal macrophages and leads to myopia, which confirmed that the presence of choroidal macrophages plays an important role in myopia development. Subsequently, based on the phenotypic characteristics of macrophages, experiments were designed to study the effects of different polarization directions of macrophages on myopia development. We found that lipopolysaccharides (LPS) injection can induce the polarization of choroidal M1 macrophages and result in myopia. Conversely, IL-4 or IL-13 injection causes choroidal M2 macrophage polarization and suppresses the progression of myopia. Additionally, we demonstrated that the opposite effects of M1 and M2 macrophages on myopia development may be related to their impacts on inflammation and oxidative stress response. These findings establish that choroidal macrophages are critically important in the development of myopia and provide new strategies for the development of myopic therapies.

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Depletion and Reconstitution of Macrophages in Mice

Cited by 5 publications

References 0 publications

Macrophage-based therapy for intervertebral disc herniation: preclinical proof-of-concept

Macrophage-based therapy for intervertebral disc herniation: preclinical proof-of-concept

Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation

The orientation of choroidal macrophage polarization significantly influences the development of myopia in murine models

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