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Human and Animal Monocytes and Macrophages in Homeostasis and Disease: 5th Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 10947

Special Issue Editors

Prof. Dr. Jacek Z. Kubiak

E-Mail Website
Guest Editor
Dynamics and Mechanics of Epithelia Group, Faculty of Medicine, Institute of Genetics and Development of Rennes, University of Rennes, CNRS, UMR 6290, 35043 Rennes, France
Interests: embryo development; cell cycle; gene regulation; cancer; stem cells; gonads; genetic diseases
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Malgorzata Kloc

E-Mail Website
Guest Editor
Transplant Immunology, The Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: macrophages; actin cytoskeleton; RhoA pathway; chronic rejection; transplantation; germ cells; stem cells; Xenopus laevis; development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Monocytes and macrophages play fundamental roles in organisms’ homeostasis and inflammatory processes, in both physiological and pathological situations. Tissue-resident macrophages participate in tissue/organ renewal, and by changing their microbicidal properties, they accommodate organism microbiota. In SARS-CoV-2 infection, monocytes and alveolar macrophages are involved in the development of the acute respiratory distress syndrome (ARDS) through the exacerbated secretion of pro-inflammatory factors. The management of this macrophage-derived cytokine storm is of paramount importance during the current COVID-19 pandemic. Another burning issue in which monocytes and macrophages play important roles is diabetes mellitus and the inflammatory processes involved in its etiology. The specialized subpopulation of macrophages, tumor-associated macrophages (TAMs), plays a role in the development and metastasis of cancer. Monocytes and macrophages are also responsible for the chronic rejection and long-term failure of transplanted organs. The efficient fight against these scourges requires a better understanding of the molecular and cellular mechanisms allowing monocytes and macrophages to underreact or overreact in their homeostatic and/or pathogen fighting roles. For this Special Issue, we invite research and review articles on recent progress in physiology and pathology linked to human and animal monocyte and macrophage functions in homeostasis and diseases.

Prof. Dr. Jacek Z. Kubiak
Prof. Dr. Malgorzata Kloc
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • monocytes
  • macrophages
  • inflammation
  • diseases
  • COVID-19
  • diabetes mellitus
  • polarity
  • phagocytosis
  • cytokine secretion
  • chemotaxis

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Published Papers (6 papers)

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Research

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16 pages, 2318 KiB  
Article
Propranolol Promotes Monocyte-to-Macrophage Differentiation and Enhances Macrophage Anti-Inflammatory and Antioxidant Activities by NRF2 Activation
by Sonia Maccari, Elisabetta Profumo, Luciano Saso, Giuseppe Marano and Brigitta Buttari
Int. J. Mol. Sci. 2024, 25(7), 3683; https://doi.org/10.3390/ijms25073683 - 26 Mar 2024
Cited by 3 | Viewed by 1252
Abstract
Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within tissue and differentiate into macrophages, which polarize to M1 or M2 macrophages with tissue-damaging or -reparative properties, respectively. This study investigates [...] Read more.
Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within tissue and differentiate into macrophages, which polarize to M1 or M2 macrophages with tissue-damaging or -reparative properties, respectively. This study investigates whether the β-adrenergic receptor (β-AR)-blocking drug propranolol modulates the monocyte-to-macrophage differentiation process and further influences macrophages in their polarization toward M1- and M2-like phenotypes. Six-day-human monocytes were cultured with M-CSF in the presence or absence of propranolol and then activated toward an M1 pro-inflammatory state or an M2 anti-inflammatory state. The chronic exposure of monocytes to propranolol during their differentiation into macrophages promoted the increase in the M1 marker CD16 and in the M2 markers CD206 and CD163 and peroxisome proliferator-activated receptor ɣ expression. It also increased endocytosis and the release of IL-10, whereas it reduced physiological reactive oxygen species. Exposure to the pro-inflammatory conditions of propranolol-differentiated macrophages resulted in an anti-inflammatory promoting effect. At the molecular level, propranolol upregulated the expression of the oxidative stress regulators NRF2, heme oxygenase-1 and NQO1. By contributing to regulating macrophage activities, propranolol may represent a novel anti-inflammatory and immunomodulating compound with relevant therapeutic potential in several inflammatory diseases. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease: 5th Edition)
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18 pages, 8095 KiB  
Article
Fever-Range Hyperthermia Promotes Macrophage Polarization towards Regulatory Phenotype M2b
by Henryk Mikołaj Kozłowski, Justyna Sobocińska, Tomasz Jędrzejewski, Bartosz Maciejewski, Artur Dzialuk and Sylwia Wrotek
Int. J. Mol. Sci. 2023, 24(24), 17574; https://doi.org/10.3390/ijms242417574 - 17 Dec 2023
Cited by 3 | Viewed by 1489
Abstract
Fever-range hyperthermia (FRH) is utilized in chronic disease treatment and serves as a model for fever’s thermal component investigation. Macrophages, highly susceptible to heat, play a pivotal role in various functions determined by their polarization state. However, it is not well recognized whether [...] Read more.
Fever-range hyperthermia (FRH) is utilized in chronic disease treatment and serves as a model for fever’s thermal component investigation. Macrophages, highly susceptible to heat, play a pivotal role in various functions determined by their polarization state. However, it is not well recognized whether this process can be modulated by FRH. To address this, we used two different macrophage cell lines that were treated with FRH. Next, to define macrophage phenotype, we examined their functional surface markers CD80 and CD163, intracellular markers such as inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), and the expression of interleukin-10 (IL-10) and tumor necrosis factor α (TNF-α). Additionally, in FRH-treated cells, we analyzed an expression of Toll-like receptor 4 (TLR-4) and its role in macrophage polarization. We also checked whether FRH can switch the polarization of macrophages in pro-inflammatory condition triggered by lipopolysaccharide (LPS). FRH induced M2-like polarization, evident in increased CD163, IL-10, and Arg-1 expression. Notably, elevated COX-2, TNF-α, and TLR-4 indicated potential pro-inflammatory properties, suggesting polarization towards the M2b phenotype. Additionally, FRH shifted lipopolysaccharide (LPS)-induced M1 polarization to an M2-like phenotype, reducing antimicrobial molecules (ROS and NO). In summary, FRH emerged as a modulator favoring M2-like macrophage polarization, even under pro-inflammatory conditions, showcasing its potential therapeutic relevance. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease: 5th Edition)
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11 pages, 2560 KiB  
Article
Anti-Inflammatory Effects of Tegoprazan in Lipopolysaccharide-Stimulated Bone-Marrow-Derived Macrophages
by Gong-Ho Han, Seong-Jun Kim, Wan-Kyu Ko, Je-Beom Hong, Seung-Hun Sheen, Min-Jai Cho and Seil Sohn
Int. J. Mol. Sci. 2023, 24(19), 14589; https://doi.org/10.3390/ijms241914589 - 26 Sep 2023
Cited by 1 | Viewed by 1573
Abstract
The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression [...] Read more.
The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease: 5th Edition)
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Review

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28 pages, 2108 KiB  
Review
Macrophages as a Source and Target of GDF-15
by Lina Susana Silva-Bermudez, Harald Klüter and Julia G. Kzhyshkowska
Int. J. Mol. Sci. 2024, 25(13), 7313; https://doi.org/10.3390/ijms25137313 - 3 Jul 2024
Viewed by 1745
Abstract
Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in [...] Read more.
Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in cancer172 and metabolic and cardiovascular disorders. Despite these clinical associations, the molecular mechanisms orchestrating its effects remain to be elucidated. The effects of GDF-15 are pleiotropic but cell-specific and dependent on the microenvironment. While GDF-15 expression can be stimulated by inflammatory mediators, its predominant effects were reported as anti-inflammatory and pro-fibrotic. The role of GDF-15 in the macrophage system has been increasingly investigated in recent years. Macrophages produce high levels of GDF-15 during oxidative and lysosomal stress, which can lead to fibrogenesis and angiogenesis at the tissue level. At the same time, macrophages can respond to GDF-15 by switching their phenotype to a tolerogenic one. Several GDF-15-based therapies are under development, including GDF-15 analogs/mimetics and GDF-15-targeting monoclonal antibodies. In this review, we summarize the major physiological and pathological contexts in which GDF-15 interacts with macrophages. We also discuss the major challenges and future perspectives in the therapeutic translation of GDF-15. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease: 5th Edition)
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19 pages, 5020 KiB  
Review
Monocytes and Macrophages in Kidney Disease and Homeostasis
by Rajesh Nachiappa Ganesh, Gabriela Garcia and Luan Truong
Int. J. Mol. Sci. 2024, 25(7), 3763; https://doi.org/10.3390/ijms25073763 - 28 Mar 2024
Viewed by 1973
Abstract
The monocyte–macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as [...] Read more.
The monocyte–macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages’ roles in different renal compartments and common renal diseases. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease: 5th Edition)
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20 pages, 1714 KiB  
Review
Invertebrate Immunity, Natural Transplantation Immunity, Somatic and Germ Cell Parasitism, and Transposon Defense
by Malgorzata Kloc, Marta Halasa, Jacek Z. Kubiak and Rafik M. Ghobrial
Int. J. Mol. Sci. 2024, 25(2), 1072; https://doi.org/10.3390/ijms25021072 - 16 Jan 2024
Cited by 1 | Viewed by 2178
Abstract
While the vertebrate immune system consists of innate and adaptive branches, invertebrates only have innate immunity. This feature makes them an ideal model system for studying the cellular and molecular mechanisms of innate immunity sensu stricto without reciprocal interferences from adaptive immunity. Although [...] Read more.
While the vertebrate immune system consists of innate and adaptive branches, invertebrates only have innate immunity. This feature makes them an ideal model system for studying the cellular and molecular mechanisms of innate immunity sensu stricto without reciprocal interferences from adaptive immunity. Although invertebrate immunity is evolutionarily older and a precursor of vertebrate immunity, it is far from simple. Despite lacking lymphocytes and functional immunoglobulin, the invertebrate immune system has many sophisticated mechanisms and features, such as long-term immune memory, which, for decades, have been exclusively attributed to adaptive immunity. In this review, we describe the cellular and molecular aspects of invertebrate immunity, including the epigenetic foundation of innate memory, the transgenerational inheritance of immunity, genetic immunity against invading transposons, the mechanisms of self-recognition, natural transplantation, and germ/somatic cell parasitism. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease: 5th Edition)
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