Immunophenotypical characterization and influence on liver homeostasis of depleting and repopulating hepatic macrophages in rats injected with clodronate

Pervin, Munmun; Golbar, Hossain M.; Bondoc, Alexandra; Izawa, Takeshi; Kuwamura, Mitsuru; Yamate, Jyoji

doi:10.1016/j.etp.2015.11.003

Cited by 24 publications

(34 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The values of AST and ALT are significantly elevated (Fig. 4), and factors for macrophage induction/activation, such as MCP-1, CSF-1, IL-6 and IL-4, are increased transiently at early stages after the injection, whereas anti-inflammatory factors such as IL-10 and TGF-β1 remain significantly decreased under hepatic macrophage depletion 43) .…”

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 98%

“…Dichloromethylene diphosphonate clodronate belongs to the family bisphosphonate used for treatment of osteolytic bone diseases and osteoporosis 41) . Once ingested by macrophages, the clodronate causes damage to macrophages via apoptosis, resulting in their depletion/disappearance 42,43) . Hepatic macrophages in rats are easily depleted by an intravenous injection of liposome-encapsulated clodoronate 44,45) .…”

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 99%

“…It is interesting to note that clodoranete treatment induces hepatic macrophage depletion without histopathological lesions, resulting in increased values of AST and ALT 43) . As mentioned above, AST and ALT values are decreased under hepatic macrophage activation 24,40) .…”

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 99%

“…There would be chemicals capable of activating or inhibiting hepatic macrophage functions as an initial toxicity. Novel pathogenesis may be brought out in relation to hepatic macrophage functions 40,43) . The analysis of macrophage conditions in rat toxicity studies would lead to refinement of hazard characterization.…”

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 99%

“…On the other hand, regardless the presence of hepatic macrophages (approximately 20% occupation) in the liver, there is little information on hepatic macrophage-related hepatocyte damage in hepatotoxicity. As aforementioned, macrophages play important roles in liver homeostasis and have heterogeneous functions depending on microenvironments 40,43) . Importantly, infiltrating macrophages can induce tissue injury by producing cytotoxic factors, indicating the presence of pathogenesis of hepatic macrophage-mediated hepatocyte injury, or the enhancement of chemical-induced hepatocyte injury by macrophages 53) .…”

Section: -2 Involvement Of Macrophages In Hepatotoxicitymentioning

confidence: 99%

See 4 more Smart Citations

Histopathological Analysis of Rat Hepatotoxicity Based on Macrophage Functions: in Particular, an Analysis for Thioacetamide-induced Hepatic Lesions

2016

Self Cite

View full text Add to dashboard Cite

Hepatic macrophages play an important role in homeostasis. The functional abnormalities of hepatic macrophages primarily or secondarily influence chemically induced hepatotoxicity. However, the evaluation system based on their functions has not yet been established. Recently, a new concept (M1-/M2-macrophage polarization) was proposed; M1macropahges are induced by INF-γ, and show high phagocytosis/tissue damage, whereas M2-macropahges are induced by IL-4 and play roles in reparative fibrosis by releasing IL-10 and TGF-β1. In hepatogenesis, CD68-expressing M1macrophages predominantly exist in embryos; in neonates, in contrast, CD163-/CD204-expressing M2-macrophages appear along the sinusoids and mature as Kupffer cells. Activated Kupffer cells by liposome decrease AST and ALT values, whereas AST and ALT values are increased under Kupffer cells depleted with clodronate treatment. Since Kupffer cells may be involved in clearance of liver enzymes, macrophage condition should be taken into consideration when hepatotoxicity is analyzed. In TAA-induced acute hepatic lesions, INF-γ, TNF-α and IL-6 for M1-factors and IL-4 for M2factors are already increased before histopathological change; the appearance of CD68-expressing M1-macrophages and CD163-expressing M2-macrophages follows in injured centrilobular lesions, and TGF-β1 and IL-10 are increased for reparative fibrosis. CD68-expressing M1-macrophages co-express MHC class II and Iba-1, whereas CD163-expressing M2-macrophages also express CD204 and Galectin-3. Under macrophage depletion by clodoronate, TAA-treated rat livers show prolonged coagulation necrosis of hepatocytes, and then develop dystrophic calcification without reparative fibrosis. The depletion of hepatic macrophages influences hepatic lesion development. Collectively, a histopathological analysis method for hepatotoxicity according to M1-/M2-macrophage polarization would lead to the refinement of hazard characterization of chemicals in food and feed.

show abstract

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 98%

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 99%

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 99%

Section: -2 Influences On Depletion Of Hepatic Macrophages In Homeomentioning

confidence: 99%

Section: -2 Involvement Of Macrophages In Hepatotoxicitymentioning

confidence: 99%

See 3 more Smart Citations

Histopathological Analysis of Rat Hepatotoxicity Based on Macrophage Functions: in Particular, an Analysis for Thioacetamide-induced Hepatic Lesions

2016

Self Cite

View full text Add to dashboard Cite

show abstract

Participation of Tumor-Associated Myeloid Cells in Progression of Amelanotic Melanoma (RMM Tumor Line) in F344 Rats, with Particular Reference to MHC Class II- and CD163-Expressing Cells

Bondoc

Golbar

Pervin

et al. 2017

Cancer Microenvironment

View full text Add to dashboard Cite

Tumor progression is often influenced by infiltration of myeloid cells; depending on the M1- or M2-like activation status, these cells may have either inhibitory or promoting effects on tumor growth. We investigated the properties of tumor-associated myeloid cells in a previously established homotransplantable amelanotic melanoma (RMM tumor line) in F344 rats. RMM tumor nodules were allowed to reach the sizes of 0.5, 1, 2 and 3 cm, respectively. Immunohistochemistry and flow cytometry was performed for macrophage markers CD68 and CD163, and for the antigen-presenting cell marker, MHC class II. Although no significant change was observed in the number of CD68 and CD163 macrophages during RMM progression, the number of MHC class II antigen-presenting cells was reduced in 3 cm nodules. Real-time RT-PCR of laser microdissection samples obtained from RMM regions rich in MHC class II cells demonstrated high expressions of M1-like factors: IFN-γ, GM-CSF and IL-12a. Furthermore, fluorescence-activated cell sorting, followed by real-time RT-PCR for CD11b MHC class II (myeloid antigen-presenting cells), CD11b CD163 (M2 type myeloid cells), CD11b CD80 (M1 type myeloid cells) and CD11b CD11c (dendritic cells) cells was performed. Based on the levels of inflammation- and tumor progression-related factors, MHC class II antigen-presenting cells showed polarization towards M1, while CD163 macrophages, towards M2. CD80 and CD11c myeloid cells did not show clear functional polarization. Our results provide novel information on tumor-associated myeloid cells in amelanotic melanoma, and may become useful in further research on melanoma immunity.

show abstract

Why nanoparticles prefer liver macrophage cell uptake in vivo

Ngo

Ahmed

Blackadar

et al. 2022

Advanced Drug Delivery Reviews

105

View full text Add to dashboard Cite

Immunophenotypical characterization and influence on liver homeostasis of depleting and repopulating hepatic macrophages in rats injected with clodronate

Cited by 24 publications

References 39 publications

Histopathological Analysis of Rat Hepatotoxicity Based on Macrophage Functions: in Particular, an Analysis for Thioacetamide-induced Hepatic Lesions

Histopathological Analysis of Rat Hepatotoxicity Based on Macrophage Functions: in Particular, an Analysis for Thioacetamide-induced Hepatic Lesions

Participation of Tumor-Associated Myeloid Cells in Progression of Amelanotic Melanoma (RMM Tumor Line) in F344 Rats, with Particular Reference to MHC Class II- and CD163-Expressing Cells

Why nanoparticles prefer liver macrophage cell uptake in vivo

Contact Info

Product

Resources

About