Aging results in accumulation of M1 and M2 hepatic macrophages and a differential response to gadolinium chloride

Bloomer, Steven A.; Moyer, Eric D.; Brown, Kyle E.; Kregel, Kevin C.

doi:10.1007/s00418-019-01827-y

Cited by 20 publications

(21 citation statements)

References 53 publications

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“…Double-labeling experiments did not demonstrate a shift in polarization with iron treatment ( Figure 4 ); similar numbers of M1 (iNOS + /HO-1 + ) and M2 (CD163 + /HO-1 + ) macrophages were observed between young and young iron-treated animals. As demonstrated previously [ 15 ], the majority of macrophages in each group were positive for both the polarization marker (iNOS or CD163) and HO-1 ( Figure 4 ). The percentage of iNOS + /HO-1 + cells in young and young iron-administered rats was 92.3% and 92.9%, respectively (not significant).…”

Section: Resultssupporting

confidence: 84%

“…For this purpose, young (6 month-old) Fischer 344 rats were treated with iron dextran, a modality that, in relatively low doses, causes iron deposition primarily in hepatic macrophages. This iron deposition mimics what has been observed in aged rats [ 14 ], and aging is associated with an increase in liver macrophage number [ 15 , 16 , 17 , 18 ]. However, it is unknown whether the excess iron serves as the proliferative stimulus [ 19 ], leading to a greater number of macrophages.…”

Section: Introductionsupporting

confidence: 75%

“…In young and young, iron-treated animals, the percentages of CD163 + /HO-1 + cells were 98.5% and 97%, respectively (not significant). It should be noted that this same labeling technique successfully detected an alteration in polarization in response to gadolinium chloride in aged rats in a previous investigation [ 15 ].…”

Section: Resultsmentioning

confidence: 81%

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Hepatic Macrophage Abundance and Phenotype in Aging and Liver Iron Accumulation

Bloomer

2022

IJMS

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Liver macrophages serve important roles in iron homeostasis through phagocytosis of effete erythrocytes and the export of iron into the circulation. Conversely, intracellular iron can alter macrophage phenotype. Aging increases hepatic macrophage number and nonparenchymal iron, yet it is unknown whether age-related iron accumulation alters macrophage number or phenotype. To evaluate macrophages in a physiological model of iron loading that mimicked biological aging, young (6 mo) Fischer 344 rats were given one injection of iron dextran (15 mg/kg), and macrophage number and phenotype were evaluated via immunohistochemistry. A separate group of old (24 mo) rats was treated with 200 mg/kg deferoxamine every 12 h for 4 days. Iron administration to young rats resulted in iron concentrations that matched the values and pattern of tissue iron deposition observed in aged animals; however, iron did not alter macrophage number or phenotype. Aging resulted in significantly greater numbers of M1 (CD68+) and M2 (CD163+) macrophages in the liver, but neither macrophage number nor phenotype were affected by deferoxamine. Double-staining experiments demonstrated that both M1 (iNOS+) and M2 (CD163+) macrophages contained hemosiderin, suggesting that macrophages of both phenotypes stored iron. These results also suggest that age-related conditions other than iron excess are responsible for the accumulation of hepatic macrophages with aging.

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Section: Resultssupporting

confidence: 84%

Section: Introductionsupporting

confidence: 75%

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Hepatic Macrophage Abundance and Phenotype in Aging and Liver Iron Accumulation

Bloomer

2022

IJMS

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“…Increasing evidence revealed a critical role of macrophage in the development and progression of diseases. 16,26,27 Deng et al 16 observed a significant increase of macrophage in the whole process of acute kidney injury to chronic kidney disease. Zhao et al 27 evaluated macrophage polarization in experimental silicosis mouse model.…”

Section: Discussionmentioning

confidence: 99%

The preventive effects of colony‐stimulating factor 1 receptor (CSF‐1R) inhibition on bladder outlet obstruction induced remodeling

Wang

Sun

Gao

et al. 2022

Neurourology and Urodynamics

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Introduction Bladder outlet obstruction (BOO) is a common problem that can affect bladder structure and function. Currently, there is no effective drugs available to prevent BOO‐induced remodeling. Previous reports have demonstrated that the pathogenesis of BOO is associated with macrophage infiltration and polarization, which is physiologically dependent on colony‐stimulating factor 1 receptor (CSF‐1R) activation. Here we utilized a highly selective CSF‐1R inhibitor, GW2580, to determine its preventive effects on BOO‐induced remodeling. Methods A total of 24 Sprague–Dawley rats were randomly divided into sham, BOO + vehicle, and BOO + GW2580 group. GW2580 or vehicle control was administrated by oral gavage at daily doses of 40 mg/kg for 6 weeks. Bladder samples were collected for histopathology, immunohistochemistry, immunofluorescence, western blotting, and flow cytometry analysis. Results Our results demonstrated that bladder fibrosis was ameliorated by GW2580 compared with the vehicle group (22.01% ± 5.13% vs. 32.15% ± 7.24%, p < 0.01). Furthermore, treatment with GW2580 induced an inhibition of macrophage infiltration (4.41% ± 1.28% vs. 13.57% ± 3.42%, p < 0.001) and M2 macrophage polarization (10.67% ± 4.15% vs. 28.59% ± 6.38%, p < 0.001). There was also a decrease of profibrotic F4/80+ α‐smooth muscle actin+ (α‐SMA+) macrophage to myofibroblast transition (9.11% ± 2.58% vs. 17.33% ± 4.01%, p < 0.001) and CD163+TGF‐β1+ cells (7.68% ± 2.10% vs. 14.17% ± 4.09%, p < 0.01) in the GW2580 group when compared with the vehicle group. Conclusions In summary, our findings showed that GW2580 is a worthwhile candidate for a follow‐up study to test in the treatment of BOO‐induced remodeling.

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“…Alterations in the tissue microenvironment in which macrophages are located can result in phenotypic changes (also known as polarization). Since aging is associated with an enhanced pro-inflammatory and pro-oxidative state environment, Bloomer et al (2020) have now expanded upon earlier studies (Bloomer et al 2009;Hilmer et al 2007;Maseo-Diaz et al 2018) to perform a detailed histochemical and morphometric characterization of macrophage phenotype in aged animals. Macrophage subtypes were determined by careful evaluation of immunostaining using well validated antibodies (see Materials and methods section of manuscript for description of detailed antibody validation).…”

Section: Mandms (1 and 2) In The Liver Of Aging Ratsmentioning

confidence: 99%

In focus in HCB

Taatjes

Roth

2020

Histochem Cell Biol

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In this first Editorial of 2020 we are pleased to highlight three Original Papers, describing the role and regulation of the tight junction proteins lipolysis-stimulated lipoprotein receptor (LSR) and tricellulin (TRIC) in human pancreatic cancer cells, an investigation of the morphological appearance and cellular behavior of clonal human breast cancer cells overexpressing β4-N-acetyl-galactosaminyltransferase 4, and the cellular analysis of macrophage phenotypes in aged rats. As you peruse this Editorial and the other contents of this issue, we would like to take the opportunity to wish you all the best for the New Year.

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Aging results in accumulation of M1 and M2 hepatic macrophages and a differential response to gadolinium chloride

Cited by 20 publications

References 53 publications

Hepatic Macrophage Abundance and Phenotype in Aging and Liver Iron Accumulation

Hepatic Macrophage Abundance and Phenotype in Aging and Liver Iron Accumulation

The preventive effects of colony‐stimulating factor 1 receptor (CSF‐1R) inhibition on bladder outlet obstruction induced remodeling

In focus in HCB

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