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Human and Animal Monocytes and Macrophages in Homeostasis and Disease

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: closed (31 January 2021) | Viewed by 32234

Special Issue Editors


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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
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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

Special Issue Information

Dear Colleagues,

Monocytes and macrophages play fundamental roles in organisms’ homeostasis and inflammatory processes, both in physiological and pathological situations. Tissue-resident macrophages participate in tissue/organ renewal and by changing their microbicidal properties accommodate organism microbiota. In SARS-CoV-2 infection, monocytes and alveolar macrophages are involved, through the exacerbated secretion of pro-inflammatory factors, in the development of the acute respiratory distress syndrome (ARDS). The management of this macrophage-derived cytokine storm is paramount 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 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. Malgorzata Kloc
Prof. Dr. Jacek Z Kubiak
Guest Editors

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Keywords

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

Published Papers (8 papers)

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Editorial

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3 pages, 192 KiB  
Editorial
The Role of Monocytes and Macrophages in Homeostasis and Disease and Novel Avenues for Putative Treatments
by Malgorzata Kloc and Jacek Z. Kubiak
Int. J. Mol. Sci. 2021, 22(9), 4927; https://doi.org/10.3390/ijms22094927 - 06 May 2021
Cited by 2 | Viewed by 1548
Abstract
Macrophages were discovered in the 19th century by Ukrainian biologist Élie Metchnikoff who worked in Ukraine, Russia, and France [...] Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)

Research

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22 pages, 27654 KiB  
Article
Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
by Thansita Bhunyakarnjanarat, Kanyarat Udompornpitak, Wilasinee Saisorn, Bhumdhanin Chantraprapawat, Peerapat Visitchanakun, Cong Phi Dang, Jiraphorn Issara-Amphorn and Asada Leelahavanichkul
Int. J. Mol. Sci. 2021, 22(3), 1377; https://doi.org/10.3390/ijms22031377 - 29 Jan 2021
Cited by 25 | Viewed by 3015
Abstract
A high dose of NSAIDs, a common analgesic, might induce lupus activity through several NSAIDs adverse effects including gastrointestinal permeability defect (gut leakage) and endotoxemia. Indomethacin (25 mg/day) was orally administered for 7 days in 24-wk-old Fc gamma receptor IIb deficient (FcgRIIb-/-) mice, [...] Read more.
A high dose of NSAIDs, a common analgesic, might induce lupus activity through several NSAIDs adverse effects including gastrointestinal permeability defect (gut leakage) and endotoxemia. Indomethacin (25 mg/day) was orally administered for 7 days in 24-wk-old Fc gamma receptor IIb deficient (FcgRIIb-/-) mice, an asymptomatic lupus model (increased anti-dsDNA without lupus nephritis), and age-matched wild-type (WT) mice. Severity of indomethacin-induced enteropathy in FcgRIIb-/- mice was higher than WT mice as demonstrated by survival analysis, intestinal injury (histology, immune-deposition, and intestinal cytokines), gut leakage (FITC-dextran assay and endotoxemia), serum cytokines, and lupus characteristics (anti-dsDNA, renal injury, and proteinuria). Prominent responses of FcgRIIb-/- macrophages toward lipopolysaccharide (LPS) compared to WT cells due to the expression of only activating-FcgRs without inhibitory-FcgRIIb were demonstrated. Extracellular flux analysis indicated the greater mitochondria activity (increased respiratory capacity and respiratory reserve) in FcgRIIb-/- macrophages with a concordant decrease in glycolysis activity when compared to WT cells. In conclusion, gut leakage-induced endotoxemia is more severe in indomethacin-administered FcgRIIb-/- mice than WT, possibly due to the enhanced indomethacin toxicity from lupus-induced intestinal immune-deposition. Due to a lack of inhibitory-FcgRIIb expression, mitochondrial function, and cytokine production of FcgRIIb-/- macrophages were more prominent than WT cells. Hence, lupus disease-activation from NSAIDs-enteropathy-induced gut leakage is possible. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)
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20 pages, 2382 KiB  
Article
The Influence of New Silicate Cement Mineral Trioxide Aggregate (MTA Repair HP) on Metalloproteinase MMP-2 and MMP-9 Expression in Cultured THP-1 Macrophages
by Katarzyna Barczak, Mirona Palczewska-Komsa, Mariusz Lipski, Dariusz Chlubek, Jadwiga Buczkowska-Radlińska and Irena Baranowska-Bosiacka
Int. J. Mol. Sci. 2021, 22(1), 295; https://doi.org/10.3390/ijms22010295 - 30 Dec 2020
Cited by 11 | Viewed by 2474
Abstract
The aim of the present study was to investigate the new silicate cement mineral trioxide aggregate (MTA Repair HP) with respect to its effect on the inflammation process involving the tooth and periodontal tissues. The composition of MTA Repair HP was supplemented with [...] Read more.
The aim of the present study was to investigate the new silicate cement mineral trioxide aggregate (MTA Repair HP) with respect to its effect on the inflammation process involving the tooth and periodontal tissues. The composition of MTA Repair HP was supplemented with plasticizer agents which can have a negative effect on the modulation of tooth inflammation. The silicate-based material in question is widely used in regeneration of the pulp-dentin complex, treatment of perforations of various locations in the tooth, as well as in surgical treatment of the complications of periapical tissue. The improved bioceramic restorative cement can affect the expression of metalloproteinases MMP-2 and MMP-9 in monocytes/macrophages involved in modulation of inflammation and regenerative processes of the tooth and periodontal tissues. The novel aspect of the present study lies in the application of the model of THP-1 monocyte/macrophage and applying the biomaterial in direct contact with the cells. Hence, it provides a representation of clinical conditions with respect to regenerative pulp and periodontal treatment with the use of MTA Repair HP. A lack of macrophage activation (as measured with flow cytometry) was found. Moreover, the study identified a lack of expression stimulation of the studied metalloproteinases (with the use of Western blotting and fluorescent microscopy). Similarly, no increase in MMP-2 and MMP-9 concentration was found (measured by ELISA method) in vitro when incubated with MTA Repair HP. Based on the results it can be concluded that new MTA Repair HP does not increase the inflammatory response in monocytes/macrophages associated with the activity of the described enzymes. It can also be speculated that they do not affect the process of dentin regeneration in which MMP-2 and MMP-9 play significant roles. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)
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11 pages, 808 KiB  
Article
AGE-RAGE Axis Stimulates Oxidized LDL Uptake into Macrophages through Cyclin-Dependent Kinase 5-CD36 Pathway via Oxidative Stress Generation
by Hironori Yashima, Michishige Terasaki, Ami Sotokawauchi, Takanori Matsui, Yusaku Mori, Tomomi Saito, Naoya Osaka, Hideki Kushima, Munenori Hiromura, Makoto Ohara, Tomoyasu Fukui and Sho-ichi Yamagishi
Int. J. Mol. Sci. 2020, 21(23), 9263; https://doi.org/10.3390/ijms21239263 - 04 Dec 2020
Cited by 11 | Viewed by 2808
Abstract
Advanced glycation end products (AGEs) are localized in macrophage-derived foam cells within atherosclerotic lesions, which could be associated with the increased risk of atherosclerotic cardiovascular disease under diabetic conditions. Although foam cell formation of macrophages has been shown to be enhanced by AGEs, [...] Read more.
Advanced glycation end products (AGEs) are localized in macrophage-derived foam cells within atherosclerotic lesions, which could be associated with the increased risk of atherosclerotic cardiovascular disease under diabetic conditions. Although foam cell formation of macrophages has been shown to be enhanced by AGEs, the underlying molecular mechanism remains unclear. Since cyclin-dependent kinase 5 (Cdk5) is reported to modulate inflammatory responses in macrophages, we investigated whether Cdk5 could be involved in AGE-induced CD36 gene expression and foam cell formation of macrophages. AGEs significantly increased Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and Cdk5 and CD36 gene expression in U937 human macrophages, all of which were inhibited by DNA aptamer raised against RAGE (RAGE-aptamer). Cdk5 and CD36 gene expression levels were correlated with each other. An antioxidant, N-acetyl-l-cysteine, mimicked the effects of RAGE-aptamer on AGE-exposed U937 cells. A selective inhibitor of Cdk5, (R)-DRF053, attenuated the AGE-induced Dil-ox-LDL uptake and CD36 gene expression, whereas anti-CD36 antibody inhibited the Dil-ox-LDL uptake but not Cdk5 gene expression. The present study suggests that AGEs may stimulate ox-LDL uptake into macrophages through the Cdk5–CD36 pathway via RAGE-mediated oxidative stress. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)
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23 pages, 6981 KiB  
Article
Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization, in Possible Relation to Damage-Associated Molecular Patterns and Autophagy
by Yuka Tsuji, Mizuki Kuramochi, Hossain M. Golbar, Takeshi Izawa, Mitsuru Kuwamura and Jyoji Yamate
Int. J. Mol. Sci. 2020, 21(23), 8998; https://doi.org/10.3390/ijms21238998 - 26 Nov 2020
Cited by 20 | Viewed by 3683
Abstract
Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver [...] Read more.
Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68+ M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-g and TNF-α, whereas CD163+ M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204+ macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B+ autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)
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Review

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18 pages, 1329 KiB  
Review
Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis
by Hui Wang, Tian Tian and Jinhua Zhang
Int. J. Mol. Sci. 2021, 22(16), 8470; https://doi.org/10.3390/ijms22168470 - 06 Aug 2021
Cited by 122 | Viewed by 8904
Abstract
Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor [...] Read more.
Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)
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13 pages, 2726 KiB  
Review
Role of Macrophages and RhoA Pathway in Atherosclerosis
by Malgorzata Kloc, Ahmed Uosef, Jacek Z. Kubiak and Rafik Mark Ghobrial
Int. J. Mol. Sci. 2021, 22(1), 216; https://doi.org/10.3390/ijms22010216 - 28 Dec 2020
Cited by 20 | Viewed by 3318
Abstract
The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages [...] Read more.
The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages and the components of the RhoA pathway are attractive targets for anti-atherosclerotic therapies, which would inhibit macrophage influx and inflammatory phenotype, maintain an anti-inflammatory environment, and promote tissue remodeling and repair. Here, we discuss the recent findings on the role of macrophages and RhoA pathway in the atherosclerotic plaque formation and resolution and the novel therapeutic approaches. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)
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14 pages, 941 KiB  
Review
Macrophage Proinflammatory Responses to Microorganisms and Transplanted Organs
by Malgorzata Kloc, Ahmed Uosef, Jacek Z. Kubiak and Rafik M. Ghobrial
Int. J. Mol. Sci. 2020, 21(24), 9669; https://doi.org/10.3390/ijms21249669 - 18 Dec 2020
Cited by 11 | Viewed by 5407
Abstract
Tissue-resident macrophages and those conscripted from the blood/bone marrow are professional phagocytes. They play a role in tissue homeostasis, replacement, and healing, and are the first-line responders to microbial (viral, bacterial, and fungi) infections. Intrinsic ameboid-type motility allows non-resident macrophages to move to [...] Read more.
Tissue-resident macrophages and those conscripted from the blood/bone marrow are professional phagocytes. They play a role in tissue homeostasis, replacement, and healing, and are the first-line responders to microbial (viral, bacterial, and fungi) infections. Intrinsic ameboid-type motility allows non-resident macrophages to move to the site of inflammation or injury, where, in response to the inflammatory milieu they perform the anti-microbial and/or tissue repair functions. Depending on the need and the signaling from the surrounding tissue and other immune cells, macrophages acquire morphologically and functionally different phenotypes, which allow them to play either pro-inflammatory or anti-inflammatory functions. As such, the macrophages are also the major players in the rejection of the transplanted organs making an excellent target for the novel anti-rejection therapies in clinical transplantation. In this review, we describe some of the less covered aspects of macrophage response to microbial infection and organ transplantation. Full article
(This article belongs to the Special Issue Human and Animal Monocytes and Macrophages in Homeostasis and Disease)
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