Macrophages in Health and Non-infectious Disease 4.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 8791

Special Issue Editor


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Guest Editor
N.N. Blokhin Cancer Research Center, Institute of Carcinogenesis, 115478 Moscow, Russia
Interests: macrophages; regulation of homeostasis; tumor associated macrophages; chronic inflammation; macrophage plasticity; macrophage molecular markers
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Special Issue Information

Dear Colleagues,

Having first been described more than 100 years ago, macrophages are still the focus of biomedical research. For about 50 years, they were considered solely part of the defense against pathogens intruding an organism; however, unravelling the mechanisms of inflammatory reaction regulation made it clear that macrophages not only possess effector functions but also act as important regulators of inflammation. A new boost was given to macrophage research in the last decade of the 20th century with the most essential study conducted in the lab of Siamon Gordon, which demonstrated alternative macrophage activation. This was a milestone in understanding macrophage function, and since that publication, a variety of macrophage markers and functional peculiarities have been described, and it has become clear that in a healthy organism, macrophages actively contribute to homeostasis and regulate processes of tolerance. Another intriguing subject is the complex interaction of tissue macrophages with resident microbiomes. This phenomenon contributes to the normal functioning of the gastrointestinal tract but also plays an important role in other organs. Apart from infectious diseases, it has been demonstrated that macrophages are actively involved in the pathogenesis of socially important non-infectious diseases, such as atherosclerosis, cancer, and diabetes. These findings have, as expected, led to the identification of macrophages as potential and highly attractive therapeutic targets. In this Special Issue, we aim to collect the most recent publications on the mechanisms that macrophages use to regulate homeostasis and their involvement in the pathogenesis of non-infectious diseases. We also welcome research describing novel macrophage markers that reflect their functional state or are involved in macrophage tolerance and training, as well as the interaction of macrophages with resident microbiomes.

Dr. Alexei Gratchev
Guest Editor

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Keywords

  • homeostasis
  • macrophage training and tolerance
  • tumor-associated macrophages
  • chronic inflammation
  • non-infectious diseases
  • microbiome

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Published Papers (4 papers)

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Research

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22 pages, 6934 KiB  
Article
Mixed-Culture Propagation of Uterine-Tissue-Resident Macrophages and Their Expression Properties of Steroidogenic Molecules
by Kazushige Ogawa and Takashi Tanida
Biomedicines 2023, 11(3), 985; https://doi.org/10.3390/biomedicines11030985 - 22 Mar 2023
Cited by 3 | Viewed by 1896
Abstract
Tissue-resident macrophages (Mø) play tissue/organ-specific roles, and the physiological/pathological implications of uterine Mø in fertility and infertility are not yet fully understood. Herein, we report a simple propagation method for tissue-resident Mø by mixed culture with the respective tissue/organ-residing cells as the niche. [...] Read more.
Tissue-resident macrophages (Mø) play tissue/organ-specific roles, and the physiological/pathological implications of uterine Mø in fertility and infertility are not yet fully understood. Herein, we report a simple propagation method for tissue-resident Mø by mixed culture with the respective tissue/organ-residing cells as the niche. We successfully propagated mouse uterine Mø by mixed culture with fibroblastic cells that exhibited properties of endometrial stromal cells. Propagated mouse uterine Mø were CD206- and arginase-1-positive; iNOS- and MHC-II-negative, indicating M2 polarization; and highly phagocytic, similar to endometrial Mø. Furthermore, uterine Mø were observed to express steroidogenic molecules including SRD5A1 and exhibited gap junction formation, likely with endometrial stromal cells. Accordingly, uterine Mø propagated by mixed culture may provide a new tool for studying immune–endocrine interactions related to fertility and infertility, particularly androgen’s intracrine actions in preparing the uterine tissue environment to support implantation and pregnancy as well as in the etiology of endometriosis. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 4.0)
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10 pages, 3395 KiB  
Article
Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex
by Rafael Nambo-Venegas, Berenice Palacios-González, Jaime Mas-Oliva, Ana Karen Aurioles-Amozurrutia, Armando Cruz-Rangel, Abel Moreno, Alfredo Hidalgo-Miranda, Mauricio Rodríguez-Dorantes, Felipe Vadillo-Ortega, Juan Xicohtencatl-Cortes, María Isabel Ruiz-Olmedo and Juan Pablo Reyes-Grajeda
Biomedicines 2023, 11(2), 490; https://doi.org/10.3390/biomedicines11020490 - 8 Feb 2023
Cited by 3 | Viewed by 2012
Abstract
Background: M1 macrophages involved in pro-inflammatory processes can be induced by low-density lipoproteins (LDL), giving rise to foam cells. In the atheroma plaque, it has been identified that males present more advanced lesions associated with infiltration. Therefore, our study aims to investigate sex-related [...] Read more.
Background: M1 macrophages involved in pro-inflammatory processes can be induced by low-density lipoproteins (LDL), giving rise to foam cells. In the atheroma plaque, it has been identified that males present more advanced lesions associated with infiltration. Therefore, our study aims to investigate sex-related changes in the transcriptome of M1 macrophages during the internalization process of LDL particles. Methods: Peripheral blood mononuclear cells (PBMCs) from healthy male and female subjects were separated using Hystopaque, and monocytes were isolated from PBMCs using a positive selection of CD14+ cells. Cells were stimulated with LDL 10 µg/mL, and the transcriptional profile of M1 macrophages performed during LDL internalization was determined using a Clariom D platform array. Results: Chromosome Y influences the immune system and inflammatory responses in males expressing 43% of transcripts in response to LDL treatment. Males and females share 15 transcripts, where most correspond to non-coding elements involved in oxidative stress and endothelial damage. Conclusions: During LDL internalization, male monocyte-derived M1 macrophages display more marked proinflammatory gene expression. In contrast, female M1 macrophages display a more significant number of markers associated with cell damage. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 4.0)
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21 pages, 11090 KiB  
Article
Eph/Ephrin Promotes the Adhesion of Liver Tissue-Resident Macrophages to a Mimicked Surface of Liver Sinusoidal Endothelial Cells
by Sho Kohara and Kazushige Ogawa
Biomedicines 2022, 10(12), 3234; https://doi.org/10.3390/biomedicines10123234 - 12 Dec 2022
Cited by 4 | Viewed by 1940
Abstract
Kupffer cells are maintained via self-renewal in specific microenvironmental niches, primarily the liver sinusoidal endothelial cells (LSECs). In this study, we propagated tissue-resident macrophages (Mø) from mouse liver using mixed culture with hepatic fibroblastic cells. Propagated liver Mø express Id3, Lxra and [...] Read more.
Kupffer cells are maintained via self-renewal in specific microenvironmental niches, primarily the liver sinusoidal endothelial cells (LSECs). In this study, we propagated tissue-resident macrophages (Mø) from mouse liver using mixed culture with hepatic fibroblastic cells. Propagated liver Mø express Id3, Lxra and Spic transcription factors, which are required for Kupffer cell characterization. Thus, Kupffer cell properties are likely to be maintained in liver Mø propagated using mixed culture with fibroblastic cells. We revealed (i) gene expression of certain Eph receptors and ephrin ligands including EphA2, ephrin-A1, EphB4, and ephrin-B1 in propagated liver Mø and primary LSECs, (ii) immunohistochemical localization of these Eph/ephrin member molecules indicating common expression in Kupffer cells and LSECs, and (iii) surface expression of several integrin α and β subunits, including α4β1, αLβ2, αMβ2, and αXβ2 integrin in propagated liver Mø and that of the corresponding ligands ICAM-1 and VCAM-1 in primary LSECs. Moreover, EphA/ephrin-A and EphB/ephrin-B interactions promoted liver Mø adhesion to the ICAM-1-adsorbed surface, which mimicked that of LSECs and may be implicated in the residence of Kupffer cells in the liver sinusoid. Further studies on regulating the residence and regeneration of Kupffer cells in related hepatic disorders are required to validate our findings. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 4.0)
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Review

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21 pages, 1789 KiB  
Review
Hepatic Macrophages as Targets for the MSC-Based Cell Therapy in Non-Alcoholic Steatohepatitis
by Irina V. Kholodenko and Konstantin N. Yarygin
Biomedicines 2023, 11(11), 3056; https://doi.org/10.3390/biomedicines11113056 - 14 Nov 2023
Cited by 2 | Viewed by 2274
Abstract
Non-alcoholic steatohepatitis (NASH) is a serious public health issue associated with the obesity pandemic. Obesity is the main risk factor for the non-alcoholic fatty liver disease (NAFLD), which progresses to NASH and then to end-stage liver disease. Currently, there are no specific pharmacotherapies [...] Read more.
Non-alcoholic steatohepatitis (NASH) is a serious public health issue associated with the obesity pandemic. Obesity is the main risk factor for the non-alcoholic fatty liver disease (NAFLD), which progresses to NASH and then to end-stage liver disease. Currently, there are no specific pharmacotherapies of NAFLD/NASH approved by the FDA or other national regulatory bodies and the treatment includes lifestyle adjustment and medicines for improving lipid metabolism, enhancing sensitivity to insulin, balancing oxidation, and counteracting fibrosis. Accordingly, further basic research and development of new therapeutic approaches are greatly needed. Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles prevent induced hepatocyte death in vitro and attenuate NASH symptoms in animal models of the disease. They interact with hepatocytes directly, but also target other liver cells, including Kupffer cells and macrophages recruited from the blood flow. This review provides an update on the pathogenesis of NAFLD/NASH and the key role of macrophages in the development of the disease. We examine in detail the mechanisms of the cross-talk between the MSCs and the macrophages, which are likely to be among the key targets of MSCs and their derivatives in the course of NAFLD/NASH cell therapy. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 4.0)
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