Special Issue "Macrophages in Health and Non-infectious Disease 2.0"

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

Deadline for manuscript submissions: 15 December 2021.

Special Issue Editors

Dr. Alexei Gratchev
E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Alexander N. Orekhov
E-Mail Website
Guest Editor
1. Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, 125315 Moscow, Russia
2. Laboratory of Infection Pathology and Molecular Microecology, Institute of Human Morphology, 3 Tsyurupa Street, 117418 Moscow, Russia
Interests: atherosclerosis; mitophagy; atherogenicity; atherosclerosis; autoantibodies; inflammation; innate immunity; cell test; macrophage; membrane transport; modified low density lipoprotein; monocyte; transcriptome; trans-sialydase; enzymatic test; cytokine; epigenetics
Special Issues, Collections and Topics in MDPI journals
Dr. Evgeny E. Bezsonov
E-Mail Website
Guest Editor
1. Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
2. Laboratory of Cellular and Molecular Pathology of Cardiovascular System, A.P. Avtsyn Research Institute of Human Morphology, 117418 Moscow, Russia
3. Department of Biology and General Genetics, I.M. Sechenov First Moscow State Medical University (Sechenov University),105043 Moscow, Russia
Interests: atherosclerosis; mitophagy; atherogenicity; atherosclerosis; autoantibodies; inflammation; innate immunity; amyloid
Special Issues, Collections and Topics in MDPI journals

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 as 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 essential study conducted in the lab of Siamon Gordon, which demonstrated alternative macrophage activation. This was a literal milestone in understanding macrophage function. 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 a 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, diabetes and others. These findings have expectedly led to the identification of macrophages as potential and highly attractive therapeutic targets. In this Special Issue, we want 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
Prof. Dr. Alexander N. Orekhov
Dr. Evgeny E. Bezsonov
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 papers will be 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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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

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Published Papers (17 papers)

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Research

Jump to: Review

Article
Candida albicans Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
Biomedicines 2021, 9(11), 1567; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111567 - 29 Oct 2021
Cited by 1 | Viewed by 308
Abstract
Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by [...] Read more.
Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by opportunistic pathogens. Candida albicans is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by C. albicans in macrophage foaming and the associated inflammation is poorly understood. We investigated whether C. albicans induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed C. albicans (HKCA). HKCA-induced lipid accumulation in macrophages along with increased expression of inflammatory markers, including CD11b and CD11c or expression and secretion of IL-1β. HKCA also increased the expression of PPARγ, CD36, and FABP4 in macrophages. Mechanistically, we found that the foamy and inflammatory macrophage phenotype induced by HKCA requires FABP4 because disruption of FABP4 in macrophages either by chemical inhibitor BMS309404 or small interfering RNA (siRNA) abrogated foam cell formation and expression of inflammatory markers CD11b, CD11c, and IL-1β. Furthermore, HKCA-treated macrophages displayed high expression and secretion of MMP-9. Inhibition of FABP4 resulted in suppression of HCKA-induced MMP-9 production. Overall, our results demonstrate that C. albicans induces foam cell formation, inflammation, and MMP-9 expression in macrophages via the upregulation of FABP4, which may constitute a novel therapeutic target for treating C. albicans-induced atherosclerosis. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
Increased Lipid Peroxidation May Be Linked to Ferritin Levels Elevation in Adult-Onset Still’s Disease
Biomedicines 2021, 9(11), 1508; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111508 - 20 Oct 2021
Viewed by 303
Abstract
Lipid peroxidation (LPO) and hyper-ferritinemia are involved in inflammatory responses. Although hyper-ferritinemia is a characteristic of AOSD, its link to LPO remains unclear. We investigated the association between LPO and ferritin expression, and evaluated the relationship between LPO-related metabolites and inflammatory parameters. Mean [...] Read more.
Lipid peroxidation (LPO) and hyper-ferritinemia are involved in inflammatory responses. Although hyper-ferritinemia is a characteristic of AOSD, its link to LPO remains unclear. We investigated the association between LPO and ferritin expression, and evaluated the relationship between LPO-related metabolites and inflammatory parameters. Mean fluorescence intensity (MFI) of LPO (C11-Biodipy581/591)-expressing PBMCs/monocytes in AOSD patients and healthy control (HC) subjects was determined by flow-cytometry analysis. Expression of ferritin and cytokines on PBMCs/macrophages was examined by immunoblotting. Plasma levels of LPO-related metabolites and cytokines were determined by ELISA and the MULTIPLEX platform, respectively. LPO MFI on PBMCs/monocytes were significantly higher in patients (median 4456 and 9091, respectively) compared with HC (1900, p < 0.05, and 4551, p < 0.01, respectively). Patients had higher ferritin expression on PBMCs (mean fold, 1.02) than HC (0.55, p < 0.05). Their ferritin expression levels on PBMCs stimulated with LPO inducers erastin or RSL3 (2.47 or 1.61, respectively) were higher than HC (0.84, p < 0.05, or 0.74, p < 0.01). Ferritin expression on erastin-treated/IL-1β-treated macrophages from patients were higher than those from HC (p < 0.001). The elevated levels of LPO-related metabolites, including malondialdehyde and 4-hydroxyalkenals, were positively correlated with disease activity scores, suggesting LPO involvement in AOSD pathogenesis. Increased ferritin expression on PBMCs/macrophages stimulated with LPO inducers indicates a link between LPO and elevated ferritin. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages
Biomedicines 2021, 9(10), 1432; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101432 - 10 Oct 2021
Viewed by 398
Abstract
The purpose of this study is to elucidate the anti-inflammatory effect of lobeglitazone (LOBE) in lipopolysaccharide (LPS)-induced bone-marrow derived macrophages (BMDMs). We induced nitric oxide (NO) production and pro-inflammatory gene expression through LPS treatment in BMDMs. The changes of NO release and expression [...] Read more.
The purpose of this study is to elucidate the anti-inflammatory effect of lobeglitazone (LOBE) in lipopolysaccharide (LPS)-induced bone-marrow derived macrophages (BMDMs). We induced nitric oxide (NO) production and pro-inflammatory gene expression through LPS treatment in BMDMs. The changes of NO release and expression of pro-inflammatory mediators by LOBE were assessed via NO quantification assay and a real-time quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, the regulatory effect of LOBE on activation of mitogen-activated protein kinase (MAPK) signaling pathway was investigated by measuring the phosphorylation state of extracellular regulatory protein (ERK) and c-Jun N-terminal kinase (JNK) proteins by Western blot. Our results show that LOBE significantly reduced LPS-induced NO production and pro-inflammatory gene expression of interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and monocyte chemoattractant protein-1 (MCP-1). Moreover, LOBE reduced phosphorylation levels of ERK and JNK of MAPK signaling pathway. In conclusion, LOBE exerts an anti-inflammatory effect in LPS-induced BMDMs by suppression of NO production and pro-inflammatory gene expression, and this effect is potentially through inhibition of the MARK signaling pathway. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
Cell Properties of Lung Tissue-Resident Macrophages Propagated by Co-Culture with Lung Fibroblastic Cells from C57BL/6 and BALB/c Mice
Biomedicines 2021, 9(9), 1241; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091241 - 16 Sep 2021
Viewed by 526
Abstract
Tissue-resident macrophages (Mø) originating from foetal precursors are maintained by self-renewal under tissue/organ-specific microenvironments (niches). We recently developed a simple propagation method applicable to tissue-resident Mø by co-culturing. Here, we examined the properties of lung tissue-resident Mø propagated by co-culturing with lung interstitial [...] Read more.
Tissue-resident macrophages (Mø) originating from foetal precursors are maintained by self-renewal under tissue/organ-specific microenvironments (niches). We recently developed a simple propagation method applicable to tissue-resident Mø by co-culturing. Here, we examined the properties of lung tissue-resident Mø propagated by co-culturing with lung interstitial cells. The intracardially and intratracheally perfused lung from BALB/c and C57BL/6 mice could minimise the contamination of alveolar Mø and lung monocytes. Lung tissue-resident Mø could be largely propagated under standard culture media along with the propagation of lung interstitial cells demonstrating a fibroblastic morphology. Propagated lung Mø showed characteristic expression properties for Mø/monocyte markers: high expressions of CD11b, CD64 and CD206; substantial expressions of Mertk; and negative expressions of Ly6C, MHC II and Siglec-F. These properties fit with those of lung interstitial Mø of a certain population that can undergo self-renewal. Propagated fibroblastic cells by co-culturing with lung Mø possessed niche properties such as Csf1 and Tgfb1 expression. Propagated lung Mø from both the mouse types were polarised to an M2 phenotype highly expressing arginase 1 without M2 inducer treatment, whereas the M1 inducers significantly increased the iNOS-positive cell percentages in C57BL/6 mice relative to those in BALB/c mice. This is the first study to demonstrate fundamental properties of lung tissue-resident Mø propagated by co-culturing. Propagated lung Mø showing features of lung interstitial Mø can serve as an indispensable tool for investigating SARS-CoV-2 diseases, although lung interstitial Mø have gained little attention in terms of their involvement in SARS-CoV-2 disease pathology, in contrast to alveolar and recruited Mø. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice
Biomedicines 2021, 9(9), 1129; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091129 - 01 Sep 2021
Viewed by 710
Abstract
Background: Macrophages play a key role in liver regeneration. The fates of resident macrophages after 70% resection are poorly investigated. In this work, using the MARCO macrophage marker (abbreviated from macrophage receptor with collagenous structure), we studied the dynamics of mouse liver resident [...] Read more.
Background: Macrophages play a key role in liver regeneration. The fates of resident macrophages after 70% resection are poorly investigated. In this work, using the MARCO macrophage marker (abbreviated from macrophage receptor with collagenous structure), we studied the dynamics of mouse liver resident macrophages after 70% resection. Methods: In BALB/c male mice, a model of liver regeneration after 70% resection was reproduced. The dynamics of markers CD68, TIM4, and MARCO were studied immunohistochemically and by using a Western blot. Results: The number of MARCO- and CD68-positive macrophages in the regenerating liver increased 1 day and 3 days after resection, respectively. At the same time, the content of the MARCO protein increased in the sorted macrophages of the regenerating liver on the third day. Conclusions: The data indicate that the number of MARCO-positive macrophages in the regenerating liver increases due to the activation of MARCO synthesis in the liver macrophages. The increased expression of MARCO by macrophages can be regarded as a sign of their activation. In the present study, stimulation with LPS led to an increase in the expression of the Marco gene in both Kupffer cells and macrophages of bone marrow origin. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
Glucose-Dependent Insulinotropic Polypeptide Suppresses Foam Cell Formation of Macrophages through Inhibition of the Cyclin-Dependent Kinase 5-CD36 Pathway
Biomedicines 2021, 9(7), 832; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070832 - 16 Jul 2021
Viewed by 715
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation [...] Read more.
Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation of, and CD36 expression in, macrophages extracted from GIP receptor-deficient (Gipr−/−) and Gipr+/+ mice and cultured human U937 macrophages by using an agonist for GIP receptor, [D-Ala2]GIP(1–42). Foam cell formation evaluated by esterification of free cholesterol to cholesteryl ester and CD36 gene expression in macrophages isolated from Gipr+/+ mice infused subcutaneously with [D-Ala2]GIP(1–42) were significantly suppressed compared with vehicle-treated mice, while these beneficial effects were not observed in macrophages isolated from Gipr−/− mice infused with [D-Ala2]GIP(1–42). When macrophages were isolated from Gipr+/+ and Gipr−/− mice, and then exposed to [D-Ala2]GIP(1–42), similar results were obtained. [D-Ala2]GIP(1–42) attenuated ox-LDL uptake of, and CD36 gene expression in, human U937 macrophages as well. Gene expression level of cyclin-dependent kinase 5 (Cdk5) was also suppressed by [D-Ala2]GIP(1–42) in U937 cells, which was corelated with that of CD36. A selective inhibitor of Cdk5, (R)-DRF053 mimicked the effects of [D-Ala2]GIP(1–42) in U937 cells. The present study suggests that GIP could inhibit foam cell formation of macrophages by suppressing the Cdk5-CD36 pathway via GIP receptor. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
Phenotypic and Functional Heterogeneity of Low-Density and High-Density Human Lung Macrophages
Biomedicines 2021, 9(5), 505; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050505 - 04 May 2021
Cited by 1 | Viewed by 668
Abstract
Background: Pulmonary macrophages are a highly heterogeneous cell population distributed in different lung compartments. Methods: We separated two subpopulations of macrophages from human lung parenchyma according to flotation over density gradients. Results: Two-thirds 65.4% of the lung macrophages have a density between 1.065 [...] Read more.
Background: Pulmonary macrophages are a highly heterogeneous cell population distributed in different lung compartments. Methods: We separated two subpopulations of macrophages from human lung parenchyma according to flotation over density gradients. Results: Two-thirds 65.4% of the lung macrophages have a density between 1.065 and 1.078 (high-density macrophages: HDMs), and the remaining one-third (34.6) had a density between 1.039 and 1.052 (low-density macrophages: LDMs). LDMs had a larger area (691 vs. 462 μm2) and cell perimeter (94 vs. 77 μm) compared to HDMs. A significantly higher percentage of HDMs expressed CD40, CD45, and CD86 compared to LDMs. In contrast, a higher percentage of LDMs expressed the activation markers CD63 and CD64. The release of TNF-α, IL-6, IL-10 and IL-12 induced by lipopolysaccharide (LPS) was significantly higher in HDMs than in LDMs. Conclusion: The human lung contains two subpopulations of macrophages that differ in buoyancy, morphometric parameters, surface marker expression and response to LPS. These subpopulations of macrophages probably play distinct roles in lung inflammation and immune responses. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Communication
The Effects of Macrophage Phenotype on Osteogenic Differentiation of MSCs in the Presence of Polyethylene Particles
Biomedicines 2021, 9(5), 499; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050499 - 01 May 2021
Viewed by 762
Abstract
Wear debris generated from the bearing surfaces of joint arthroplasties leads to acute and chronic inflammation, which is strongly associated with implant failure. Macrophages derived from monocytes recruited to the local tissues have a significant impact on bone healing and regeneration. Macrophages can [...] Read more.
Wear debris generated from the bearing surfaces of joint arthroplasties leads to acute and chronic inflammation, which is strongly associated with implant failure. Macrophages derived from monocytes recruited to the local tissues have a significant impact on bone healing and regeneration. Macrophages can adopt various functional phenotypes. While M1 macrophages are pro-inflammatory, M2 macrophages express factors important for tissue repair. Here, we established a 3D co-culture system to investigate how the immune system influences the osteogenic differentiation of mesenchymal stem cells (MSCs) in the presence of micron-sized particles. This system allowed for the simulation of an inflammatory reaction via the addition of Lipopolysaccharide-contaminated polyethylene particles (cPE) and the characterization of bone formation using micro-CT and gene and protein expression. Co-cultures of MSCs with M2 macrophages in the presence of cPE in a 3D environment resulted in the increased expression of osteogenic markers, suggesting facilitation of bone formation. In this model, the upregulation of M2 macrophage expression of immune-associated genes and cytokines contributes to enhanced bone formation by MSCs. This study elucidates how the immune system modulates bone healing in response to an inflammatory stimulus using a unique 3D culture system. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
Carnosine Protects Macrophages against the Toxicity of Aβ1-42 Oligomers by Decreasing Oxidative Stress
Biomedicines 2021, 9(5), 477; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050477 - 26 Apr 2021
Cited by 3 | Viewed by 808
Abstract
Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous peptide widely distributed in excitable tissues such as the brain. This dipeptide has well-known antioxidant, anti-inflammatory, and anti-aggregation activities, and it may be useful for treatment of neurodegenerative disorders such as Alzheimer’s disease (AD). In this [...] Read more.
Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous peptide widely distributed in excitable tissues such as the brain. This dipeptide has well-known antioxidant, anti-inflammatory, and anti-aggregation activities, and it may be useful for treatment of neurodegenerative disorders such as Alzheimer’s disease (AD). In this disease, peripheral infiltrating macrophages play a substantial role in the clearance of amyloid beta (Aβ) peptides from the brain. Correspondingly, in patients suffering from AD, defects in the capacity of peripheral macrophages to engulf Aβ have been reported. The effects of carnosine on macrophages and oxidative stress associated with AD are consequently of substantial interest for drug discovery in this field. In the present work, a model of stress induced by Aβ1-42 oligomers was investigated using a combination of methods including trypan blue exclusion, microchip electrophoresis with laser-induced fluorescence, flow cytometry, fluorescence microscopy, and high-throughput quantitative real-time PCR. These assays were used to assess the ability of carnosine to protect macrophage cells, modulate oxidative stress, and profile the expression of genes related to inflammation and pro- and antioxidant systems. We found that pre-treatment of RAW 264.7 macrophages with carnosine counteracted cell death and apoptosis induced by Aβ1-42 oligomers by decreasing oxidative stress as measured by levels of intracellular nitric oxide (NO)/reactive oxygen species (ROS) and production of peroxynitrite. This protective activity of carnosine was not mediated by modulation of the canonical inflammatory pathway but instead can be explained by the well-known antioxidant and free-radical scavenging activities of carnosine, enhanced macrophage phagocytic activity, and the rescue of fractalkine receptor CX3CR1. These new findings obtained with macrophages challenged with Aβ1-42 oligomers, along with the well-known multimodal mechanism of action of carnosine in vitro and in vivo, substantiate the therapeutic potential of this dipeptide in the context of AD pathology. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Article
Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin E2
Biomedicines 2021, 9(5), 449; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050449 - 21 Apr 2021
Viewed by 572
Abstract
Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E2 (PGE2) released [...] Read more.
Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E2 (PGE2) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE2 to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE2 synthesis. PGE2 in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE2 in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Review

Jump to: Research

Review
Pathological Significance of Macrophages in Erectile Dysfunction Including Peyronie’s Disease
Biomedicines 2021, 9(11), 1658; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111658 - 10 Nov 2021
Viewed by 352
Abstract
Erectile function is regulated by complex mechanisms centered on vascular- and nerve-related systems. Hence, dysregulation of these systems leads to erectile dysfunction (ED), which causes mental distress and decreases the quality of life of patients and their partners. At the molecular level, many [...] Read more.
Erectile function is regulated by complex mechanisms centered on vascular- and nerve-related systems. Hence, dysregulation of these systems leads to erectile dysfunction (ED), which causes mental distress and decreases the quality of life of patients and their partners. At the molecular level, many factors, such as fibrosis, lipid metabolism abnormalities, the immune system, and stem cells, play crucial roles in the etiology and development of ED. Although phosphodiesterase type 5 (PDE5) inhibitors are currently the standard treatment agents for patients with ED, they are effective only in a subgroup of patients. Therefore, further insight into the pathological mechanism underlying ED is needed to discuss ED treatment strategies. In this review, we focused on the biological and pathological significance of macrophages in ED because the interaction of macrophages with ED-related mechanisms have not been well explored, despite their important roles in vasculogenic and neurogenic diseases. Furthermore, we examined the pathological significance of macrophages in Peyronie’s disease (PD), a cause of ED characterized by penile deformation (visible curvature) during erection and pain. Although microinjury and the subsequent abnormal healing process of the tunica albuginea are known to be important processes in this disease, the detailed etiology and pathophysiology of PD are not fully understood. This is the first review on the pathological role of macrophages in PD. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Review
Two Faces of Macrophages: Training and Tolerance
Biomedicines 2021, 9(11), 1596; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111596 - 02 Nov 2021
Viewed by 381
Abstract
Macrophages are present in almost all body tissues. They detect and quickly respond to “environmental signals” in the tissue. Macrophages have been associated with numerous beneficial roles, such as host defense, wound healing, and tissue regeneration; however, they have also been linked to [...] Read more.
Macrophages are present in almost all body tissues. They detect and quickly respond to “environmental signals” in the tissue. Macrophages have been associated with numerous beneficial roles, such as host defense, wound healing, and tissue regeneration; however, they have also been linked to the development of diverse illnesses, particularly cancers and autoimmune disorders. Complex signaling, epigenetic, and metabolic pathways drive macrophage training and tolerance. The induced intracellular program differs depending on the type of initial stimuli and the tissue microenvironment. Due to the essential roles of macrophages in homeostatic and their association with the pathogenesis of inflammatory diseases, recent studies have investigated the molecular mechanisms of macrophage training and tolerance. This review discusses the role of factors involved in macrophage training and tolerance, along with the current studies in human diseases. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Review
Macrophages and Iron: A Special Relationship
Biomedicines 2021, 9(11), 1585; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111585 - 30 Oct 2021
Viewed by 311
Abstract
Macrophages perform a variety of different biological functions and are known for their essential role in the immune response. In this context, a principal function is phagocytic clearance of pathogens, apoptotic and senescent cells. However, the major targets of homeostatic phagocytosis by macrophages [...] Read more.
Macrophages perform a variety of different biological functions and are known for their essential role in the immune response. In this context, a principal function is phagocytic clearance of pathogens, apoptotic and senescent cells. However, the major targets of homeostatic phagocytosis by macrophages are old/damaged red blood cells. As such, macrophages play a crucial role in iron trafficking, as they recycle the large quantity of iron obtained by hemoglobin degradation. They also seem particularly adapted to handle and store amounts of iron that would be toxic to other cell types. Here, we examine the specific and peculiar iron metabolism of macrophages. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Review
The Role of Microglia in the Development of Neurodegenerative Diseases
Biomedicines 2021, 9(10), 1449; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101449 - 12 Oct 2021
Viewed by 458
Abstract
Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this [...] Read more.
Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Review
Macrophage Identification In Situ
Biomedicines 2021, 9(10), 1393; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101393 - 04 Oct 2021
Viewed by 424
Abstract
Understanding the processes of inflammation and tissue regeneration after injury is of great importance. For a long time, macrophages have been known to play a central role during different stages of inflammation and tissue regeneration. However, the molecular and cellular mechanisms by which [...] Read more.
Understanding the processes of inflammation and tissue regeneration after injury is of great importance. For a long time, macrophages have been known to play a central role during different stages of inflammation and tissue regeneration. However, the molecular and cellular mechanisms by which they exert their effects are as yet mostly unknown. While in vitro macrophages have been characterized, recent progress in macrophage biology studies revealed that macrophages in vivo exhibited distinctive features. Actually, the precise characterization of the macrophages in vivo is essential to develop new healing treatments and can be approached via in situ analyses. Nowadays, the characterization of macrophages in situ has improved significantly using antigen surface markers and cytokine secretion identification resulting in specific patterns. This review aims for a comprehensive overview of different tools used for in situ macrophage identification, reporter genes, immunolabeling and in situ hybridization, discussing their advantages and limitations. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Review
Cross Talk of Macrophages with Tumor Microenvironment Cells and Modulation of Macrophages in Cancer by Virotherapy
Biomedicines 2021, 9(10), 1309; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101309 - 24 Sep 2021
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Abstract
Cellular compartments constituting the tumor microenvironment including immune cells, fibroblasts, endothelial cells, and mesenchymal stromal/stem cells communicate with malignant cells to orchestrate a series of signals that contribute to the evolution of the tumor microenvironment. In this study, we will focus on the [...] Read more.
Cellular compartments constituting the tumor microenvironment including immune cells, fibroblasts, endothelial cells, and mesenchymal stromal/stem cells communicate with malignant cells to orchestrate a series of signals that contribute to the evolution of the tumor microenvironment. In this study, we will focus on the interplay in tumor microenvironment between macrophages and mesenchymal stem cells and macrophages and fibroblasts. In particular, cell–cell interaction and mediators secreted by these cells will be examined to explain pro/anti-tumor phenotypes induced in macrophages. Nonetheless, in the context of virotherapy, the response of macrophages as a consequence of treatment with oncolytic viruses will be analyzed regarding their polarization status and their pro/anti-tumor response. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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Review
Macrophages and Foam Cells: Brief Overview of Their Role, Linkage, and Targeting Potential in Atherosclerosis
Biomedicines 2021, 9(9), 1221; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091221 - 14 Sep 2021
Viewed by 479
Abstract
Atherosclerosis is still one of the main causes of death around the globe. This condition leads to various life-threatening cardiovascular complications. However, no effective preventive measures are known apart from lifestyle corrections, and no cure has been developed. Despite numerous studies in the [...] Read more.
Atherosclerosis is still one of the main causes of death around the globe. This condition leads to various life-threatening cardiovascular complications. However, no effective preventive measures are known apart from lifestyle corrections, and no cure has been developed. Despite numerous studies in the field of atherogenesis, there are still huge gaps in already poor understanding of mechanisms that underlie the disease. Inflammation and lipid metabolism violations are undoubtedly the key players, but many other factors, such as oxidative stress, endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. This overview is focusing on the role of macrophages in atherogenesis, which are at the same time a part of the inflammatory response, and also tightly linked to the foam cell formation, thus taking part in both crucial for atherogenesis processes. Being essentially involved in atherosclerosis development, macrophages and foam cells have attracted attention as a promising target for therapeutic approaches. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
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