scholarly journals Airway monocyte modulation relates to TNF dysregulation in neutrophilic asthma

2021 ◽  
pp. 00131-2021
Author(s):  
Natalie M. Niessen ◽  
Peter G. Gibson ◽  
Jodie L. Simpson ◽  
Hayley A. Scott ◽  
Katherine J. Baines ◽  
...  
Keyword(s):  
Immune Cell ◽  
Blood Monocytes ◽  
Monocytes And Macrophages ◽  
Soluble Ligand ◽  
Inflammatory Phenotype ◽  
Ligand Expression ◽  
Membrane Bound ◽  
Soluble Tnf Receptor ◽  
Inflammatory Milieu ◽  
Inflammatory Phenotypes

BackgroundDysregulation of TNFα signalling is implicated in neutrophilic asthma. TNFα signalling involves membrane-bound and soluble ligand (TNFα) and receptors (TNFRs); however, little is known about how these factors are altered in asthma. We hypothesized that intercompartment-, immune cell- and/or asthma inflammatory phenotype-dependent regulation could relate to TNF factor dysregulation in neutrophilic asthma.MethodsMeasures were made in 45 adults with asthma (36 non-neutrophilic, 9 neutrophilic) and 8 non-asthma controls. Soluble TNFα, TNFR1 and TNFR2 were quantified in plasma and sputum supernatant by ELISA, and membrane-bound TNFα/TNFR1/TNFR2 measured on eosinophils, neutrophils, monocytes, and macrophages in blood and sputum by flow cytometry. Marker expression was compared between inflammatory phenotypes and compartments, and relationship of membrane-bound and soluble TNF markers and immune cell numbers tested by correlation.ResultsSoluble sputum TNFR1 and TNFR2 were increased in neutrophilic versus non-neutrophilic asthma (p=0.010 and p=0.029). Membrane-bound TNFα expression was upregulated on sputum versus blood monocytes, while TNFR1 and TNFR2 levels were reduced on airway versus blood monocytes and neutrophils. Soluble TNFR1 and TNFR2 in sputum significantly correlated with the number of airway monocytes (p=0.016, r=0.358 and p=0.029, r=0.327).ConclusionOur results imply that increased sputum soluble TNF receptor levels observed in neutrophilic asthma relate to the increased recruitment of monocytes and neutrophils into the airways and their subsequent receptor shedding. Monocytes also increase TNFα ligand expression in the airways. These results suggest an important contribution of airway monocytes to the altered inflammatory milieu in neutrophilic asthma.

scholarly journals Cdx2 regulates immune cell infiltration in the intestine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simon Chewchuk ◽  
Sanzida Jahan ◽  
David Lohnes
Keyword(s):  
Intestinal Epithelium ◽  
Target Genes ◽  
Immune Cell ◽  
Cell Number ◽  
Macrophage Infiltration ◽  
Intestinal Homeostasis ◽  
Chronic Inflammatory Response ◽  
Complex Protein ◽  
Inflammatory Phenotype

AbstractThe intestinal epithelium is a unique tissue, serving both as a barrier against pathogens and to conduct the end digestion and adsorption of nutrients. As regards the former, the intestinal epithelium contains a diverse repertoire of immune cells, including a variety of resident lymphocytes, macrophages and dendritic cells. These cells serve a number of roles including mitigation of infection and to stimulate regeneration in response to damage. The transcription factor Cdx2, and to a lesser extent Cdx1, plays essential roles in intestinal homeostasis, and acts as a context-dependent tumour suppressor in colorectal cancer. Deletion of Cdx2 from the murine intestinal epithelium leads to macrophage infiltration resulting in a chronic inflammatory response. However the mechanisms by which Cdx2 loss evokes this response are poorly understood. To better understand this relationship, we used a conditional mouse model lacking all intestinal Cdx function to identify potential target genes which may contribute to this inflammatory phenotype. One such candidate encodes the histocompatability complex protein H2-T3, which functions to regulate intestinal iCD8α lymphocyte activity. We found that Cdx2 occupies the H3-T3 promoter in vivo and directly regulates its expression via a Cdx response element. Loss of Cdx function leads to a rapid and pronounced attenuation of H2-T3, followed by a decrease in iCD8α cell number, an increase in macrophage infiltration and activation of pro-inflammatory cascades. These findings suggest a previously unrecognized role for Cdx in intestinal homeostasis through H2-T3-dependent regulation of iCD8α cells.

scholarly journals Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes

2013 ◽  
Vol 24 (14) ◽  
pp. 2186-2200 ◽  
Author(s):  
Deborah A. Flusberg ◽  
Jérémie Roux ◽  
Sabrina L. Spencer ◽  
Peter K. Sorger
Keyword(s):  
Cell Death ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Therapeutic Agents ◽  
Inflammatory Phenotype ◽  
Drug Naïve ◽  
Apoptosis Inducing Agents ◽  
Inflammatory Phenotypes ◽  
Survival Mechanisms ◽  
Necrosis Factor

When clonal populations of human cells are exposed to apoptosis-inducing agents, some cells die and others survive. This fractional killing arises not from mutation but from preexisting, stochastic differences in the levels and activities of proteins regulating apoptosis. Here we examine the properties of cells that survive treatment with agonists of two distinct death receptors, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and anti-FasR antibodies. We find that “survivor” cells are highly resistant to a second ligand dose applied 1 d later. Resistance is reversible, resetting after several days of culture in the absence of death ligand. “Reset” cells appear identical to drug-naive cells with respect to death ligand sensitivity and gene expression profiles. TRAIL survivors are cross-resistant to activators of FasR and vice versa and exhibit an NF-κB–dependent inflammatory phenotype. Remarkably, reversible resistance is induced in the absence of cell death when caspase inhibitors are present and can be sustained for 1 wk or more, also without cell death, by periodic ligand exposure. Thus stochastic differences in cell state can have sustained consequences for sen­sitivity to prodeath ligands and acquisition of proinflammatory phenotypes. The important role played by periodicity in TRAIL exposure for induction of opposing apoptosis and survival mechanisms has implications for the design of optimal therapeutic agents and protocols.

scholarly journals MORPHOLOGY AND PEROXIDASE CYTOCHEMISTRY OF MOUSE PROMONOCYTES, MONOCYTES, AND MACROPHAGES

1970 ◽  
Vol 132 (4) ◽  
pp. 794-812 ◽  
Author(s):  
Ralph van Furth ◽  
James G. Hirsch ◽  
Martha E. Fedorko
Keyword(s):  
Bone Marrow Cells ◽  
Peritoneal Macrophages ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Membrane Ruffling ◽  
Mouse Macrophages ◽  
Granular Cytoplasm ◽  
Monocytes And Macrophages ◽  
Mature Mouse ◽  
Peroxidase Cytochemistry

Mouse promonocytes have been identified and studied in cultures of bone marrow cells. These cells have a diameter of 14–20 µ, and in stained preparations reveal a large, indented or folded nucleus, and basophilic, finely granular cytoplasm. The living promonocyte viewed by phase contrast shows additional features: nucleoli, small dense bodies, and vesicles in the cytoplasm adjacent to the nuclear hilus, and slight membrane ruffling. Prominent ultrastructural components of promonocytes include a well developed Golgi apparatus, small numbers of centrosomal granules and vacuoles, extensive ribosomal aggregates, and finger-like projections of the cell surface. Promonocytes engage in pinocytosis and phagocytosis, but they are less active in these functions than are peripheral blood monocytes of peritoneal macrophages. Promonocytes are positive for peroxidase, the reaction product being localized to granules most of which are centrally situated in the cell. Monocytes in blood or in inflammatory peritoneal exudates display much smaller numbers of peroxidase-positive granules, and various types of mature mouse macrophages are peroxidase negative.

scholarly journals Effect of pregnancy hormone mixtures on cytokine production and surface marker expression in naïve and LPS-activated THP-1 differentiated monocytes/macrophages

2019 ◽  
Vol 26 (2) ◽  
pp. 84-96
Author(s):  
María Isabel Mendoza-Cabrera ◽  
Rosa-Elena Navarro-Hernández ◽  
Anne Santerre ◽  
Pablo Cesar Ortiz-Lazareno ◽  
Ana Laura Pereira-Suárez ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cytokine Production ◽  
Immune Cell ◽  
Surface Marker ◽  
Independent Manner ◽  
Surface Marker Expression ◽  
Monocytes And Macrophages ◽  
Marker Expression ◽  
Activated Monocytes ◽  
In Pregnancy

In pregnancy, maternal monocytes and macrophages acquire a specific phenotype that enables them to maintain immune tolerance and facilitate hormone–immune cell interactions, which are necessary for gestational progression. The aim of this study was to determine the effect of pregnancy hormone mixtures of the first and third trimesters on both resting and activated monocytes and macrophages. Pregnancy hormone levels (cortisol, estradiol, progesterone, and prolactin) were quantified at the first and third trimesters. The average of the levels obtained was used to prepare two mixtures of synthetic hormones: low and high. These mixtures were then used to stimulate THP-1 monocytes and macrophages, resting or activated with LPS. Cytokine production in the culture supernatants and surface marker expression (CD14, CD86, and CD163) were evaluated by ELISA and flow cytometry, respectively. We found that the hormones modulated the pro-inflammatory response of THP-1 cells, LPS-activated monocytes, and macrophages, inducing high levels of IL-10 and low levels of IL-8, IL-1-β, and IL-6. All hormone stimulation increased the CD163 receptor in both resting and LPS-activated monocytes and macrophages in a dose-independent manner, unlike CD14 and CD86. Pregnancy hormones promote the expression of the markers associated with the M2-like phenotype, modulating their pro-inflammatory response. This phenotype regulation by hormones could be a determinant in pregnancy.

scholarly journals The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 51-64 ◽  
Author(s):  
AE Gassmann ◽  
R van Furth
Keyword(s):  
Inflammatory Reaction ◽  
Peripheral Blood ◽  
Low Dose ◽  
Peritoneal Macrophages ◽  
High Dose ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Azathioprine Treatment ◽  
Monocytes And Macrophages ◽  
Kinetics Of

Abstract The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24–48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.

scholarly journals Medawar’s PostEra: Galectins Emerged as Key Players During Fetal-Maternal Glycoimmune Adaptation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ellen Menkhorst ◽  
Nandor Gabor Than ◽  
Udo Jeschke ◽  
Gabriela Barrientos ◽  
Laszlo Szereday ◽  
...  
Keyword(s):  
Immune Cell ◽  
Successful Pregnancy ◽  
Fetal Health ◽  
The Past ◽  
Mammalian Embryogenesis ◽  
Carbohydrate Ligands ◽  
Membrane Bound

Lectin-glycan interactions, in particular those mediated by the galectin family, regulate many processes required for a successful pregnancy. Over the past decades, increasing evidence gathered from in vitro and in vivo experiments indicate that members of the galectin family specifically bind to both intracellular and membrane bound carbohydrate ligands regulating angiogenesis, immune-cell adaptations required to tolerate the fetal semi-allograft and mammalian embryogenesis. Therefore, galectins play important roles in fetal development and placentation contributing to maternal and fetal health. This review discusses the expression and role of galectins during the course of pregnancy, with an emphasis on maternal immune adaptions and galectin-glycan interactions uncovered in the recent years. In addition, we summarize the galectin fingerprints associated with pathological gestation with particular focus on preeclampsia.

scholarly journals HIF1α activation in dendritic cells under sterile conditions promotes an anti-inflammatory phenotype through accumulation of intracellular lipids

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Elizabeth G. Wood ◽  
Claire E. Macdougall ◽  
Hazel Blythe ◽  
Marc Clément ◽  
Romain A. Colas ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cell Function ◽  
Immune Cell ◽  
Lipid Synthesis ◽  
Mortality And Morbidity ◽  
Intracellular Lipids ◽  
Adipose Tissue Dysfunction ◽  
Disease Mortality ◽  
Key Factor ◽  
Inflammatory Phenotype

AbstractObesity is among the leading causes of elevated cardiovascular disease mortality and morbidity. Adipose tissue dysfunction, insulin resistance and inflammation are recognized as important risk factors for the development of cardiovascular disorders in obesity. Hypoxia appears to be a key factor in adipose tissue dysfunction affecting not only adipocytes but also immune cell function. Here we examined the effect of hypoxia-induced transcription factor HIF1α activation on classical dendritic cell (cDCs) function during obesity. We found that deletion of Hif1α on cDCs results in enhanced adipose-tissue inflammation and atherosclerotic plaque formation in a mouse model of obesity. This effect is mediated by HIF1α-mediated increased lipid synthesis, accumulation of lipid droplets and alter synthesis of lipid mediators. Our findings demonstrate that HIF1α activation in cDCs is necessary to control vessel wall inflammation.

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