Editorial

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4 pages, 401 KiB

Open AccessEditorial

Monocyte and Macrophage Function Diversity

by Malgorzata Kloc and Jacek Z. Kubiak

Int. J. Mol. Sci. 2022, 23(20), 12404; https://doi.org/10.3390/ijms232012404 - 17 Oct 2022

Cited by 4 | Viewed by 1505

Abstract

In the last decade, there has been a tremendous revival of interest in monocyte and macrophages [...] Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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Research

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11 pages, 4991 KiB

Open AccessCommunication

Hepatic Macrophage Abundance and Phenotype in Aging and Liver Iron Accumulation

by Steven A. Bloomer

Int. J. Mol. Sci. 2022, 23(12), 6502; https://doi.org/10.3390/ijms23126502 - 10 Jun 2022

Cited by 3 | Viewed by 1842

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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18 pages, 4623 KiB

Open AccessArticle

The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model

by Yaser Hosny Ali Elewa, Md Abdul Masum, Sherif Kh. A. Mohamed, Md Rashedul Islam, Teppei Nakamura, Osamu Ichii and Yasuhiro Kon

Int. J. Mol. Sci. 2022, 23(8), 4449; https://doi.org/10.3390/ijms23084449 - 18 Apr 2022

Cited by 2 | Viewed by 1981

Abstract

In our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-Fas ^lpr/lpr (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clusters (MFALCs) and inflammatory lung lesions [...] Read more.

In our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-Fas ^lpr/lpr (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clusters (MFALCs) and inflammatory lung lesions compared to the male mice. However, the effect of Dex, an immunosuppressive drug, on both lung lesions and the development of MFALCs in Lpr mice has not been identified yet. Therefore, in this study, we compared the development of lung lesions and MFALCs in female Lpr mice that received either saline (saline group “SG”) or dexamethasone (dexamethasone group “DG”) in drinking water as a daily dose along with weekly intraperitoneal injections for 10 weeks. Compared to the SG group, the DG group showed a significant reduction in the levels of serum anti-dsDNA antibodies, the size of MFALCs, the degree of lung injury, the area of high endothelial venules (HEVs), and the number of proliferating and immune cells in both MFALCs and the lungs. A significant positive correlation was observed between the size of MFALCs and the cellular aggregation in the lungs of Lpr mice. Therefore, this study confirmed the ameliorative effect of Dex on the development of lung injury and MFALCs via their regressive effect on both immune cells’ proliferative activity and the development of HEVs. Furthermore, the reprogramming of MFALCs by targeting immune cells and HEVs may provide a therapeutic strategy for autoimmune-disease-associated lung injury. Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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20 pages, 4458 KiB

Open AccessArticle

Quantitative and Functional Assessment of the Influence of Routinely Used Cryopreservation Media on Mononuclear Leukocytes for Medical Research

by Patrick Haider, Timothy Hoberstorfer, Manuel Salzmann, Michael B. Fischer, Walter S. Speidl, Johann Wojta and Philipp J. Hohensinner

Int. J. Mol. Sci. 2022, 23(3), 1881; https://doi.org/10.3390/ijms23031881 - 07 Feb 2022

Cited by 3 | Viewed by 3188

Abstract

Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee similar experimental conditions. Immune cells react differently [...] Read more.

Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee similar experimental conditions. Immune cells react differently to cryopreservation, and populations and functions of immune cells change during the process of freeze–thawing. To allow for a setup that preserves cell number and function optimally, we tested four different cryopreservation media. MNCs from 15 human individuals were analyzed. Before freezing and after thawing, the distribution of leukocytes was quantified by flow cytometry. Cultured cells were stimulated using lipopolysaccharide, and their immune response was quantified by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). Ultimately, the performance of the cryopreservation media was ranked. Cell recovery and viability were different between the media. Cryopreservation led to changes in the relative number of monocytes, T cells, B cells, and their subsets. The inflammatory response of MNCs was altered by cryopreservation, enhancing the basal production of inflammatory cytokines. Different cryopreservation media induce biases, which needs to be considered when designing a study relying on cryopreservation. Here, we provide an overview of four different cryopreservation media for choosing the optimal medium for a specific task. Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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20 pages, 4827 KiB

Open AccessArticle

Enhanced Bacteremia in Dextran Sulfate-Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance

by Arthid Thim-Uam, Jiradej Makjaroen, Jiraphorn Issara-Amphorn, Wilasinee Saisorn, Dhammika Leshan Wannigama, Wiwat Chancharoenthana and Asada Leelahavanichkul

Int. J. Mol. Sci. 2022, 23(3), 1676; https://doi.org/10.3390/ijms23031676 - 31 Jan 2022

Cited by 16 | Viewed by 3471

Abstract

Because both endotoxemia and gut dysbiosis post-splenectomy might be associated with systemic infection, the susceptibility against infection was tested by dextran sulfate solution (DSS)-induced colitis and lipopolysaccharide (LPS) injection models in splenectomy mice with macrophage experiments. Here, splenectomy induced a gut barrier defect [...] Read more.

Because both endotoxemia and gut dysbiosis post-splenectomy might be associated with systemic infection, the susceptibility against infection was tested by dextran sulfate solution (DSS)-induced colitis and lipopolysaccharide (LPS) injection models in splenectomy mice with macrophage experiments. Here, splenectomy induced a gut barrier defect (FITC-dextran assay, endotoxemia, bacteria in mesenteric lymph nodes, and the loss of enterocyte tight junction) and gut dysbiosis (increased Proteobacteria by fecal microbiome analysis) without systemic inflammation (serum IL-6). In parallel, DSS induced more severe mucositis in splenectomy mice than sham-DSS mice, as indicated by mortality, stool consistency, gut barrier defect, serum cytokines, and blood bacterial burdens. The presence of green fluorescent-producing (GFP) E. coli in the spleen of sham-DSS mice after an oral gavage supported a crucial role of the spleen in the control of bacteria from gut translocation. Additionally, LPS administration in splenectomy mice induced lower serum cytokines (TNF-α and IL-6) than LPS-administered sham mice, perhaps due to LPS tolerance from pre-existing post-splenectomy endotoxemia. In macrophages, LPS tolerance (sequential LPS stimulation) demonstrated lower cell activities than the single LPS stimulation, as indicated by the reduction in supernatant cytokines, pro-inflammatory genes (iNOS and IL-1β), cell energy status (extracellular flux analysis), and enzymes of the glycolysis pathway (proteomic analysis). In conclusion, a gut barrier defect after splenectomy was vulnerable to enterocyte injury (such as DSS), which caused severe bacteremia due to defects in microbial control (asplenia) and endotoxemia-induced LPS tolerance. Hence, gut dysbiosis and gut bacterial translocation in patients with a splenectomy might be associated with systemic infection, and gut-barrier monitoring or intestinal tight-junction strengthening may be useful. Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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Review

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19 pages, 527 KiB

Open AccessReview

Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies

by Nataliya V. Mushenkova, Nikita G. Nikiforov, Nikolay K. Shakhpazyan, Varvara A. Orekhova, Nikolay K. Sadykhov and Alexander N. Orekhov

Int. J. Mol. Sci. 2022, 23(15), 8381; https://doi.org/10.3390/ijms23158381 - 29 Jul 2022

Cited by 13 | Viewed by 2974

Abstract

Chronic inflammation is implicated in numerous human pathologies. In particular, low-grade inflammation is currently recognized as an important mechanism of osteoarthritis (OA), at least in some patients. Among the signs of the inflammatory process are elevated macrophage numbers detected in the OA synovium [...] Read more.

Chronic inflammation is implicated in numerous human pathologies. In particular, low-grade inflammation is currently recognized as an important mechanism of osteoarthritis (OA), at least in some patients. Among the signs of the inflammatory process are elevated macrophage numbers detected in the OA synovium compared to healthy controls. High macrophage counts also correlate with clinical symptoms of the disease. Macrophages are central players in the development of chronic inflammation, pain, cartilage destruction, and bone remodeling. However, macrophages are also involved in tissue repair and remodeling, including cartilage. Therefore, reduction of macrophage content in the joints correlates with deleterious effects in OA models. Macrophage population is heterogeneous and dynamic, with phenotype transitions being induced by a variety of stimuli. In order to effectively use the macrophage inflammatory circuit for treatment of OA, it is important to understand macrophage heterogeneity and interactions with surrounding cells and tissues in the joint. In this review, we discuss functional phenotypes of macrophages and specific targeting approaches relevant for OA treatment development. Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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12 pages, 1648 KiB

Open AccessReview

Monocyte–Macrophage Lineage Cell Fusion

by Malgorzata Kloc, Arijita Subuddhi, Ahmed Uosef, Jacek Z. Kubiak and Rafik M. Ghobrial

Int. J. Mol. Sci. 2022, 23(12), 6553; https://doi.org/10.3390/ijms23126553 - 12 Jun 2022

Cited by 14 | Viewed by 5897

Abstract

Cell fusion (fusogenesis) occurs in natural and pathological conditions in prokaryotes and eukaryotes. Cells of monocyte–macrophage lineage are highly fusogenic. They create syncytial multinucleated giant cells (MGCs) such as osteoclasts (OCs), MGCs associated with the areas of infection/inflammation, and foreign body-induced giant cells [...] Read more.

Cell fusion (fusogenesis) occurs in natural and pathological conditions in prokaryotes and eukaryotes. Cells of monocyte–macrophage lineage are highly fusogenic. They create syncytial multinucleated giant cells (MGCs) such as osteoclasts (OCs), MGCs associated with the areas of infection/inflammation, and foreign body-induced giant cells (FBGCs). The fusion of monocytes/macrophages with tumor cells may promote cancer metastasis. We describe types and examples of monocyte–macrophage lineage cell fusion and the role of actin-based structures in cell fusion. Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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19 pages, 768 KiB

Open AccessReview

Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

by Paweł Bryniarski, Katarzyna Nazimek and Janusz Marcinkiewicz

Int. J. Mol. Sci. 2022, 23(3), 1772; https://doi.org/10.3390/ijms23031772 - 04 Feb 2022

Cited by 12 | Viewed by 3140

Abstract

This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The [...] Read more.

This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders. Full article

(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease 3.0)

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