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Molecular Mechanisms and Functions of Macrophage Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 4127

Special Issue Editor


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Guest Editor
Center of Cellular Immunotherapy, Warsaw University of Life Sciences, J. Ciszewskiego 8, b. 23, 02-786 Warsaw, Poland
Interests: macrophage cells; cell-based therapies; immunology; tumor microenvironment
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Special Issue Information

Dear Colleagues, 

Macrophages play a key role in innate and adaptive immune responses, as well as in maintaining homeostasis in normal, healthy conditions. They provide first-line defense against pathogens by recognizing, engulfing, and eventually destroying foreign invaders. On the other hand, macrophages are involved in various pathological conditions, such as atherosclerosis, fibrosis, autoimmune diseases, and metabolic syndrome. In cancer, macrophages play an important role in the whole process of tumorigenesis, impacting tumor progression, metastasis, and treatment responses. Their dual role as contributors to inflammation and promoters of tissue repair underscores the intricate nature of their involvement in disease states. The intricate roles of macrophages in health and disease are explored in our Special Issue, "Molecular Mechanisms and Functions of Macrophage Cells", that aims to unravel the complex molecular pathways shaping macrophage behavior. Identifying the molecular mechanisms governing their behavior is a crucial step for unlocking their therapeutic potential.

This Special Issue, "Molecular Mechanisms and Functions of Macrophage Cells", invites the submissions of original articles and reviews—focusing on the molecular mechanisms driving macrophage behavior and function of these cells within the context of cancer and other diseases. Exploring innovative strategies to modulate their function, identifying novel therapeutic targets within macrophages, and delving into the development of macrophages as precise therapeutic tools are of the greatest interest. Advancing our understanding of macrophage biology will pave the way for groundbreaking therapeutic strategies. Your insightful contributions to this Special Issue will broaden the landscape of immune-mediated therapeutic interventions.

We look forward to your valuable contributions to this Special Issue.

Prof. Dr. Magdalena Król
Guest Editor

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Keywords

  • macrophages
  • immune responses
  • inflammation
  • cancer
  • tumor microenvironment

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Published Papers (3 papers)

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Research

17 pages, 5275 KiB  
Article
Unveiling the Phenotypic Variability of Macrophages: Insights from Donor Diversity and Pooling Strategies
by Bartłomiej Taciak, Agnieszka Grochowska, Małgorzata Górczak, Emilia Górka, Marcin Skorzynski, Maciej Białasek, Tomasz P. Rygiel and Magdalena Król
Int. J. Mol. Sci. 2025, 26(3), 1272; https://doi.org/10.3390/ijms26031272 - 31 Jan 2025
Viewed by 813
Abstract
Macrophages are key players in inflammation and immune responses due to their phenotypic plasticity. This study examined the effects of pooling donor-derived macrophages on their phenotype and function, focusing on murine bone marrow-derived macrophages (BMDMs) and human monocyte-derived macrophages (hMDMs). Murine BMDMs were [...] Read more.
Macrophages are key players in inflammation and immune responses due to their phenotypic plasticity. This study examined the effects of pooling donor-derived macrophages on their phenotype and function, focusing on murine bone marrow-derived macrophages (BMDMs) and human monocyte-derived macrophages (hMDMs). Murine BMDMs were generated using L929-conditioned media and compared across single and pooled donors (two-to-five mice). Similarly, hMDMs cultured with M-CSF from individual donors were compared to pooled cultures. Pooling macrophages did not alter core phenotypic markers (CD11b, F4/80, CD64) or functional outputs such as cytokine secretion and nitric oxide production. In hMDMs, pooling reduced variability and led to slightly elevated or more-uniform marker expression. These findings demonstrate that pooling macrophages minimizes inter-individual variability without compromising cellular stability or function, enhancing reproducibility in immunological research while maintaining the option of single-donor studies for personalized analyses. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Functions of Macrophage Cells)
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13 pages, 1176 KiB  
Article
Evidence for a Pro-Inflammatory State of Macrophages from Non-Obese Type-2 Diabetic Goto-Kakizaki Rats
by Amanda Santos de Almeida Silveira, Amara Cassandra dos Anjos Alves, Gabriela Mandú Gimenes, Patrícia da Silva Quessada, Tiago Bertola Lobato, Beatriz Belmiro Dias, Ana Carolina Gomes Pereira, Patrícia Nancy Iser-Bem, Joice Naiara Bertaglia Pereira, Elaine Hatanaka, Laureane Nunes Masi, Tânia Cristina Pithon-Curi, Vânia Gomes de Moura Mattaraia, Sandro Massao Hirabara, Amanda Rabello Crisma, Renata Gorjão and Rui Curi
Int. J. Mol. Sci. 2024, 25(19), 10240; https://doi.org/10.3390/ijms251910240 - 24 Sep 2024
Cited by 1 | Viewed by 1460
Abstract
Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of [...] Read more.
Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of non-obese T2DM. These rats exhibit hyperglycemia beginning at weaning and exhibit lower body mass than control Wistar rats. Herein, we tested the hypothesis that macrophages of GK rats are permanently in a pro-inflammatory state, which may be associated with a systemic inflammation condition that mimics the pathogenesis of obesity-induced T2DM. Using eighteen-week-old GK and control Wistar rats, we investigated the proportions of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages isolated from the peritoneal cavity. Additionally, the production of inflammatory cytokines and reactive oxygen species (ROS) in cultured macrophages under basal and stimulated conditions was assessed. It was found that phorbol myristate acetate (PMA) stimulation increased GK rat macrophage ROS production 90-fold compared to basal levels. This response was also three times more pronounced than in control cells (36-fold). The production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), tended to be upregulated in cultured macrophages from GK rats under basal conditions. Macrophages from GK rats produced 1.6 times more granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.5 times more monocyte chemoattractant protein-1 (MCP-1) and 3.3 times more TNF-α than control cells when stimulated with lipopolysaccharide (LPS) (p = 0.0033; p = 0.049; p = 0.002, respectively). Moreover, compared to control cells, GK rats had 60% more M1 (p = 0.0008) and 23% less M2 (p = 0.038) macrophages. This study is the first to report macrophage inflammatory reprogramming towards a pro-inflammatory state in GK rats. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Functions of Macrophage Cells)
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13 pages, 9642 KiB  
Article
Immune-Enhancing Effects of Gwakhyangjeonggi-san in RAW 264.7 Macrophage Cells through the MAPK/NF-κB Signaling Pathways
by Yun Hee Jeong, Hye Jin Yang, Wei Li, You-Chang Oh and Jang-Gi Choi
Int. J. Mol. Sci. 2024, 25(17), 9246; https://doi.org/10.3390/ijms25179246 - 26 Aug 2024
Cited by 1 | Viewed by 1266
Abstract
Gwakhyangjeonggi-san (GJS) is a traditional herbal medicine used in East Asia for the treatment of symptoms involving lower intestinal abnormalities; however, the effects of GJS on innate immunity and its cellular mechanisms of action have not been elucidated. In this study, we assessed [...] Read more.
Gwakhyangjeonggi-san (GJS) is a traditional herbal medicine used in East Asia for the treatment of symptoms involving lower intestinal abnormalities; however, the effects of GJS on innate immunity and its cellular mechanisms of action have not been elucidated. In this study, we assessed the immune-enhancing activity and underlying mechanisms of GJS using RAW 264.7 murine macrophages. The results showed that GJS treatment significantly increased the secretion of nitric oxide and cytokines and their mRNA expression in macrophage RAW 264.7 cells without causing cytotoxicity. GJS treatment also significantly increased the production of reactive oxygen species, as well as inducing phagocytic activity, adhesion function, and migration ability, all of which improved the immune response. In addition, GJS activated nuclear factor-κB by promoting the phosphorylation and degradation of inhibitor of nuclear factor-κB alpha. Furthermore, GJS markedly increased the phosphorylation of mitogen-activated protein kinase in RAW 264.7 cells. These findings indicate that GJS has potential value as a dietary supplement for strengthening immunity. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Functions of Macrophage Cells)
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