scholarly journals Metabolism of tissue macrophages in homeostasis and pathology

2021 ◽  
Author(s):  
Stefanie K. Wculek ◽  
Gillian Dunphy ◽  
Ignacio Heras-Murillo ◽  
Annalaura Mastrangelo ◽  
David Sancho
Keyword(s):  
Immune Cells ◽  
Current Knowledge ◽  
Cellular Metabolism ◽  
Structural Components ◽  
Tissue Macrophage ◽  
Cellular Energy ◽  
Pathological Conditions ◽  
Macrophage Populations ◽  
Adult Bone

AbstractCellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy and structural components. The emerging field of immunometabolism highlights the importance of cellular metabolism for the maintenance and activities of immune cells. Macrophages are embryo- or adult bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome, atherosclerosis, fibrosis or cancer. Macrophage metabolism has largely been studied in vitro. However, different organs contain diverse macrophage populations that specialize in distinct and often tissue-specific functions. This context specificity creates diverging metabolic challenges for tissue macrophage populations to fulfill their homeostatic roles in their particular microenvironment and conditions their response in pathological conditions. Here, we outline current knowledge on the metabolic requirements and adaptations of macrophages located in tissues during homeostasis and selected diseases.

scholarly journals Role of Leptin in the Activation of Immune Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Patricia Fernández-Riejos ◽  
Souad Najib ◽  
Jose Santos-Alvarez ◽  
Consuelo Martín-Romero ◽  
Antonio Pérez-Pérez ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Energy Homeostasis ◽  
Humoral Factors ◽  
Endocrine Organ ◽  
Pathological Conditions ◽  
Immune Mediated ◽  
Infection Susceptibility

Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response.

A kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy has a dominant-negative impact on CSF1R signaling

2021 ◽  
Author(s):  
Jennifer Stables ◽  
Emma K. Green ◽  
Anuj Sehgal ◽  
Omkar Patkar ◽  
Sahar Keshvari ◽  
...  
Keyword(s):  
Human Disease ◽  
Bone Marrow Cells ◽  
Negative Impact ◽  
Dominant Negative ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Adult Onset ◽  
Tissue Macrophage ◽  
Macrophage Populations

AbstractAmino acid substitutions in the kinase domain of the human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (Glu631Lys; E631K) in the mouse Csf1r locus. Homozygous mutation (Csf1rE631K/E631K) phenocopied the Csf1r knockout; with prenatal mortality or severe postnatal growth retardation and hydrocephalus. Heterozygous mutation delayed the postnatal expansion of tissue macrophage populations in most organs. Bone marrow cells from Csf1rE631K/+ mice were resistant to CSF1 stimulation in vitro, and Csf1rE631K/+ mice were unresponsive to administration of a CSF1-Fc fusion protein which expands tissue macrophage populations in controls. In the brain, microglial cell numbers and dendritic arborization were reduced in the Csf1rE631K/+ mice as in ALSP patients. The microglial phenotype is the opposite of microgliosis observed in Csf1r+/- mice. However, we found no evidence of brain pathology or impacts on motor function in aged Csf1rE631K/+ mice. We conclude that disease-associated CSF1R mutations encode dominant negative repressors of CSF1R signaling. We speculate that leukoencephalopathy associated with human CSF1R mutations requires an environmental trigger and/or epistatic interaction with common neurodegenerative disease-associated alleles.Summary StatementThis study describes the effect of a human disease-associated mutation in the mouse CSF1R gene on postnatal development and growth factor responsiveness of cells of the macrophage lineage.

SHP2 drives inflammation-triggered insulin resistance by reshaping tissue macrophage populations

2021 ◽  
Vol 13 (591) ◽  
pp. eabe2587
Author(s):  
Romain Paccoud ◽  
Céline Saint-Laurent ◽  
Enzo Piccolo ◽  
Mylène Tajan ◽  
Alizée Dortignac ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Marrow ◽  
Tyrosine Phosphatase ◽  
Lipid Management ◽  
Tissue Macrophage ◽  
Depth Analysis ◽  
Macrophage Populations

Insulin resistance is a key event in type 2 diabetes onset and a major comorbidity of obesity. It results from a combination of fat excess–triggered defects, including lipotoxicity and metaflammation, but the causal mechanisms remain difficult to identify. Here, we report that hyperactivation of the tyrosine phosphatase SHP2 found in Noonan syndrome (NS) led to an unsuspected insulin resistance profile uncoupled from altered lipid management (for example, obesity or ectopic lipid deposits) in both patients and mice. Functional exploration of an NS mouse model revealed this insulin resistance phenotype correlated with constitutive inflammation of tissues involved in the regulation of glucose metabolism. Bone marrow transplantation and macrophage depletion improved glucose homeostasis and decreased metaflammation in the mice, highlighting a key role of macrophages. In-depth analysis of bone marrow–derived macrophages in vitro and liver macrophages showed that hyperactive SHP2 promoted a proinflammatory phenotype, modified resident macrophage homeostasis, and triggered monocyte infiltration. Consistent with a role of SHP2 in promoting inflammation-driven insulin resistance, pharmaceutical SHP2 inhibition in obese diabetic mice improved insulin sensitivity even better than conventional antidiabetic molecules by specifically reducing metaflammation and alleviating macrophage activation. Together, these results reveal that SHP2 hyperactivation leads to inflammation-triggered metabolic impairments and highlight the therapeutical potential of SHP2 inhibition to ameliorate insulin resistance.

The Application of Peptides in Glioma: a Novel Tool for Therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Li Li ◽  
Jianhong Chen ◽  
Yue Ming ◽  
Bin Li ◽  
Ruoqiu Fu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Therapeutic Agent ◽  
Tumor Volume ◽  
Current Knowledge ◽  
Glioma Cells ◽  
Cellular Heterogeneity ◽  
Therapeutic Approaches ◽  
The Central Nervous System ◽  
Stimulating Factor

Background: Glioma is the most aggressive and lethal tumor of the central nervous system. Owing to the cellular heterogeneity, the invasiveness, and blood-brain barrier (BBB), current therapeutic approaches, such as chemotherapy and radiotherapy, are poorly to obtain great anti-tumor efficacy. However, peptides, a novel type of therapeutic agent, displayed excellent ability in the tumor, which becomes a new molecule for glioma treatment. Method: We review the current knowledge on peptides for the treatment of glioma through a PubMed-based literature search. Results: In the treatment of glioma, peptides can be used as (i) decoration on the surface of the delivery system, facilitating the distribution and accumulation of the anti-tumor drug in the target site;(ii) anti-tumor active molecules, inhibiting the growth of glioma and reducing solid tumor volume; (iii) immune-stimulating factor, and activating immune cells in the tumor microenvironment or recruiting immune cells to the tumor for breaking out the immunosuppression by glioma cells. Conclusion: The application of peptides has revolutionized the treatment of glioma, which is based on targeting, penetrating, anti-tumor activities, and immunostimulatory. Moreover, better outcomes have been discovered in combining different kinds of peptides rather than a single one. Until now, more and more preclinical studies have been developed with multifarious peptides, which show promising results in vitro or vivo with the model of glioma.

Electron probe x-ray microanalysis and electron microscopy of amino acid absorption and transport by the small intestine: inhibition by chemical poisons and correlation to the elemental composition of the epithelial cells

1986 ◽  
Vol 44 ◽  
pp. 134-135
Author(s):  
A. J. Tousimis
Keyword(s):  
Small Intestine ◽  
Amino Acid ◽  
Epithelial Cells ◽  
Elemental Composition ◽  
Isotope Labeling ◽  
Structural Components ◽  
X Ray ◽  
Human Small Intestine ◽  
Transport Studies

The elemental composition of amino acids is similar to that of the major structural components of the epithelial cells of the small intestine and other tissues. Therefore, their subcellular localization and concentration measurements are not possible by x-ray microanalysis. Radioactive isotope labeling: I131-tyrosine, Se75-methionine and S35-methionine have been successfully employed in numerous absorption and transport studies. The latter two have been utilized both in vitro and vivo, with similar results in the hamster and human small intestine. Non-radioactive Selenomethionine, since its absorption/transport behavior is assumed to be the same as that of Se75- methionine and S75-methionine could serve as a compound tracer for this amino acid.

The Immune System Regulation in Sepsis: From Innate to Adaptive

2019 ◽  
Vol 20 (8) ◽  
pp. 799-816 ◽  
Author(s):  
Yue Qiu ◽  
Guo-wei Tu ◽  
Min-jie Ju ◽  
Cheng Yang ◽  
Zhe Luo
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Immune Cells ◽  
Current Knowledge ◽  
Systemic Inflammatory Response ◽  
Immune System Regulation

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

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