Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate

AbstractMacrophages and myeloid dendritic cells (DCs) represent alternative differentiation options of bone marrow progenitors and blood monocytes. This choice profoundly influences the immune response under normal and pathological conditions, but the underlying transcriptional events remain unresolved. Here, we show that experimental activation of the transcription factors PU.1 and MafB in transformed chicken myeloid progenitors triggered alternative DC or macrophage fate, respectively. PU.1 activation also was instructive for DC fate in the absence of cytokines in human HL-60 cell-derived myeloid progenitor and monocyte clones. Differentiation of normal human monocytes to DCs led to a rapid increase of PU.1 to high levels that preceded phenotypic changes, but no MafB expression, whereas monocyte-derived macrophages expressed MafB and only moderate levels of PU.1. DCs inducing levels of PU.1 inhibited MafB expression in monocytes, which appeared to be required for DC specification, since constitutive MafB expression inhibited DC differentiation. Consistent with this, PU.1 directly bound to MafB, inhibited its transcriptional activity in macrophages, and repressed its ability to induce macrophage differentiation in chicken myeloid progenitors. We propose that high PU.1 activity favors DCs at the expense of macrophage fate by inhibiting expression and activity of the macrophage factor MafB.

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Fine structure of the normal human parathyroid gland as revealed by thin section and freeze-fracture with regard to some pathological conditions

Ultrastructure of Endocrine Cells and Tissues ◽

10.1007/978-1-4613-3861-1_26 ◽

1984 ◽

pp. 302-312

Author(s):

Jürgen Thiele

Keyword(s):

Fine Structure ◽

Parathyroid Gland ◽

Thin Section ◽

Freeze Fracture ◽

Pathological Conditions ◽

Normal Human

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Identification of normal human peripheral blood monocytes and liver as sites of synthesis of coagulation factor XIII a-chain

Blood ◽

10.1182/blood.v70.2.579.bloodjournal702579 ◽

1987 ◽

Vol 70 (2) ◽

pp. 579-582

Author(s):

LJ Weisberg ◽

DT Shiu ◽

PR Conkling ◽

MA Shuman

Keyword(s):

Peripheral Blood ◽

Factor Xiii ◽

Human Peripheral Blood ◽

Cdna Probe ◽

Coagulation Factor ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Normal Human ◽

Normal Human Peripheral Blood ◽

A Chain

Factor XIII is the fibrin-stabilizing factor that covalently cross- links fibrin monomers to form a highly organized, stable fibrin clot. The plasma form of factor XIII is a heterodimer, a2b2, consisting of two a-chains and two b-chains; the intracellular form, such as in platelets and placenta, is a dimer, a2, consisting of a-chains only. The catalytic function of factor XIII, a transglutaminase, resides in the a-chain. To address questions regarding sites of synthesis of factor XIII a-chain, an EcoRI restriction fragment from the protein- coding region of the factor XIII a-chain cDNA was used as a probe for Northern blot analysis. The cDNA probe showed hybridization with a single approximately 4.0-kilobase (kb) message in poly (A)+ mRNA prepared from normal human peripheral blood monocytes and normal human liver. The results demonstrate conclusively that factor XIII a-chains are actively synthesized in circulating monocytes and in liver. To our knowledge, these data represent the first demonstration of synthesis of any blood coagulation factor in primary uncultured and unstimulated monocytes or macrophage cells.

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Is the myonuclear domain ceiling hypothesis dead?

Singapore Medical Journal ◽

10.11622/smedj.2021103 ◽

2021 ◽

Author(s):

F Aman ◽

E El Khatib ◽

A AlNeaimi ◽

A Mohamed ◽

AS Almulla ◽

...

Keyword(s):

Satellite Cells ◽

Transcriptional Activity ◽

Muscle Hypertrophy ◽

Muscle Fibres ◽

Adaptation Process ◽

Muscle Adaptation ◽

Upper Limit ◽

Pathological Conditions ◽

Myonuclear Domain ◽

Multinuclear Cells

Muscle fibres are multinuclear cells, and the cytoplasmic territory where a single myonucleus controls transcriptional activity is called the myonuclear domain (MND). MND size shows flexibility during muscle hypertrophy. The MND ceiling hypothesis states that hypertrophy results in the expansion of MND size to an upper limit or MND ceiling, beyond which additional myonuclei via activation of satellite cells are required to support further growth. However, the debate about the MND ceiling hypothesis is far from settled, and various studies show conflicting results about the existence or otherwise of MND ceiling in hypertrophy. The aim of this review is to summarise the literature about the MND ceiling in various settings of hypertrophy and discuss the possible factors contributing to a discrepancy in the literature. We conclude by describing the physiological and clinical significance of the MND ceiling limit in the muscle adaptation process in various physiological and pathological conditions.

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Synthesis of a peroxidase activity by the cells of hairy cell leukemia: a study by ultrastructural cytochemistry

Blood ◽

10.1182/blood.v52.3.537.537 ◽

1978 ◽

Vol 52 (3) ◽

pp. 537-550 ◽

Cited By ~ 31

Author(s):

F Reyes ◽

MF Gourdin ◽

JP Farcet ◽

B Dreyfus ◽

J Breton-Gorius

Keyword(s):

Peroxidase Activity ◽

Hairy Cell Leukemia ◽

Cell Types ◽

Human Monocytes ◽

Hairy Cell ◽

Blood Monocytes ◽

Cell Leukemia ◽

Data Points ◽

Normal Human ◽

Hairy Cells

Abstract The nature of cells present in the blood, marrow, and spleen of patients with hairy cell leukemia is largely debated. These cells have been tentatively categorized on the basis of either monocytic or lymphocytic markers, and the accumulating data points to the fact that they share some characteristics of both cell types. Although hairy cells are known to lack myeloperoxidase-positive granules, present in normal human monocytes, we investigated the possible presence of other peroxidase activities differing from the granule-bound myeloperoxidase. The study was carried out with several methods based on the incubation of fixed and unfixed cells in the presence of diaminobenzidine and hydrogen peroxide. A peroxidase activity was found in hairy cells, located always in the endoplasmic reticulum but not in the Golgi apparatus or in any granule. By its cytochemical characteristics it appears to be closely related to that of tissue macrophages, activated blood monocytes, and other nonlymphocytic hematopoietic cells. This peroxidase is not found in lymphocytes with B or T phenotypes.

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The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy

Autophagy ◽

10.1080/15548627.2019.1578040 ◽

2019 ◽

Vol 15 (7) ◽

pp. 1150-1162 ◽

Cited By ~ 8

Author(s):

Meichao Zhang ◽

Furao Liu ◽

Pingting Zhou ◽

Qian Wang ◽

Ci Xu ◽

...

Keyword(s):

Signaling Pathway ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Macrophage Differentiation ◽

Myeloid Progenitors

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Whole Transcriptome Analysis of Myeloid Dendritic Cells Reveals Distinct Genetic Regulation in Patients with Allergies

International Journal of Molecular Sciences ◽

10.3390/ijms21228640 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8640

Author(s):

Kijeong Lee ◽

Mi-Ryung Han ◽

Ji Woo Yeon ◽

Byoungjae Kim ◽

Tae Hoon Kim

Keyword(s):

Dendritic Cells ◽

Transcriptome Sequencing ◽

Genetic Regulation ◽

Genetic Alterations ◽

Limited Information ◽

Blood Monocytes ◽

Sequencing Data ◽

Myeloid Dendritic Cells ◽

Th2 Immune Response ◽

Whole Transcriptome

Dendritic cells (DCs) play critical roles in atopic diseases, orchestrating both innate and adaptive immune systems. Nevertheless, limited information is available regarding the mechanism through which DCs induce hyperresponsiveness in patients with allergies. This study aims to reveal novel genetic alterations and future therapeutic target molecules in the DCs from patients with allergies using whole transcriptome sequencing. Transcriptome sequencing of human BDCA-3+/CD11c+ DCs sorted from peripheral blood monocytes obtained from six patients with allergies and four healthy controls was conducted. Gene expression profile data were analyzed, and an ingenuity pathway analysis was performed. A total of 1638 differentially expressed genes were identified at p-values < 0.05, with 11 genes showing a log2-fold change ≥1.5. The top gene network was associated with cell death/survival and organismal injury/abnormality. In validation experiments, amphiregulin (AREG) showed consistent results with transcriptome sequencing data, with increased mRNA expression in THP-1-derived DCs after Der p 1 stimulation and higher protein expression in myeloid DCs obtained from patients with allergies. This study suggests an alteration in the expression of DCs in patients with allergies, proposing related altered functions and intracellular mechanisms. Notably, AREG might play a crucial role in DCs by inducing the Th2 immune response.

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Inonotus obliquus Extracts Decreased Expression of MMP1 mRNA via JNK-AP-1 Axis

Cosmetics ◽

10.3390/cosmetics7020036 ◽

2020 ◽

Vol 7 (2) ◽

pp. 36

Author(s):

Young Joo Kim ◽

Hwa Jun Cha

Keyword(s):

Oxidative Stress ◽

Matrix Metalloproteinases ◽

Mrna Expression ◽

Transcriptional Activity ◽

Dermal Fibroblasts ◽

Human Dermal Fibroblasts ◽

Inonotus Obliquus ◽

The Family ◽

Normal Human ◽

Normal Human Dermal Fibroblasts

Inonotus obliquus, which is parasitic on birch and other trees, is a fungus in the family Hymenochaetaceae. In this study, we investigated whether Inonotus obliquus extracts used in traditional medicine were decreased in the expression of matrix metalloproteinases-1 (MMP-1) in the normal human dermal fibroblasts. As shown in our results, extracts of Inonotus obliquus decreased MMP1 expression in oxidative stress-exposed normal human dermal fibroblasts. Additionally, Inonotus obliquus extracts decreased AP-1 transcriptional activity and phospho-JNK in oxidative stress-exposed normal human dermal fibroblasts. Oxidative stress mediated the elevation of MMP1 mRNA expression and was well regulated by the JNK-AP-1 axis. Therefore, the results suggest that Inonotus obliquus extracts decreased MMP1 mRNA expression by regulating JNK-AP-1 axis. Additionally, Inonotus obliquus extracts have the potential to reduce collagen destruction and the formation of wrinkles and to be used as a cosmetic ingredient.

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EFFECT OF NORMAL AND ACTIVATED HUMAN MACROPHAGES ON TOXOPLASMA GONDII

Journal of Experimental Medicine ◽

10.1084/jem.139.5.1154 ◽

1974 ◽

Vol 139 (5) ◽

pp. 1154-1174 ◽

Cited By ~ 77

Author(s):

Seth E. Anderson ◽

Jack S. Remington

Keyword(s):

Toxoplasma Gondii ◽

Cell Mediated Immunity ◽

Blood Monocytes ◽

Effector Cells ◽

Human Macrophages ◽

Obligate Intracellular ◽

Normal Human ◽

Induction Of Resistance ◽

In Vitro Induction

Human macrophages derived from in vitro culture of peripheral blood monocytes were studied under a variety of conditions to determine their microbicidal capacity for the obligate intracellular protozoan, Toxoplasma gondii. The effect of macrophages on intracellular Toxoplasma was evaluated morphologically by light and phase microscopy and by autoradiography. When macrophages from dye test (DT)-negative or DT-positive individuals were infected with Toxoplasma in the presence of normal human serum, the organisms were able to multiply intracellularly with resultant destruction of the monolayer. Once organisms were intracellular, the presence of antibody-containing serum in the medium did not alter this inability of the macrophages to kill Toxoplasma. However, when Toxoplasma were incubated in the presence of heat-inactivated DT-positive serum just before infection of the monolayers, the intracellular organisms were inhibited or killed by normal macrophages. Attempts were made to activate macrophages in vitro to kill Toxoplasma. Macrophages incubated in the presence of sensitized lymphocytes and Streptokinase-Streptodornase (SK-SD) or Toxoplasma lysate antigen (TLA) were found to kill Toxoplasma when compared to macrophages incubated in the presence of lymphocytes from DT-negative individuals and TLA or lymphocytes alone. Thus, in vitro induction of resistance (both specifically and nonspecifically) in human macrophages was accomplished by culturing these cells in the presence of specifically sensitized lymphocytes and antigen. These results suggest that, as in the mouse model, activated human macrophages have the ability to inhibit or kill intracellular Toxoplasma and that these cells may be important as effector cells in cell-mediated immunity (CMI) to toxoplasmosis in man.

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