scholarly journals Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival

2014 ◽  
Vol 211 (8) ◽  
pp. 1525-1531 ◽  
Author(s):  
Emmanuel L. Gautier ◽  
Stoyan Ivanov ◽  
Jesse W. Williams ◽  
Stanley Ching-Cheng Huang ◽  
Genevieve Marcelin ◽  
...  
Keyword(s):  
Peritoneal Macrophage ◽  
Endocrine Cells ◽  
Marked Decrease ◽  
Peritoneal Macrophages ◽  
Alternative Activation ◽  
Activation Markers ◽  
Normal Number ◽  
Proliferation And Differentiation ◽  
Resident Peritoneal Macrophage ◽  
Metabolic Regulators

The transcription factor Gata6 regulates proliferation and differentiation of epithelial and endocrine cells and cancers. Among hematopoietic cells, Gata6 is expressed selectively in resident peritoneal macrophages. We thus examined whether the loss of Gata6 in the macrophage compartment affected peritoneal macrophages, using Lyz2-Cre x Gata6flox/flox mice to tackle this issue. In Lyz2-Cre x Gata6flox/flox mice, the resident peritoneal macrophage compartment, but not macrophages in other organs, was contracted, with only a third the normal number of macrophages remaining. Heightened rates of death explained the marked decrease in peritoneal macrophage observed. The metabolism of the remaining macrophages was skewed to favor oxidative phosphorylation and alternative activation markers were spontaneously and selectively induced in Gata6-deficient macrophages. Gene expression profiling revealed perturbed metabolic regulators, including aspartoacylase (Aspa), which facilitates generation of acetyl CoA. Mutant mice lacking functional Aspa phenocopied the higher propensity to death and led to a contraction of resident peritoneal macrophages. Thus, Gata6 regulates differentiation, metabolism, and survival of resident peritoneal macrophages.

scholarly journals MECHANISM OF ACTION OF MIGRATION INHIBITORY FACTOR (MIF)

1972 ◽  
Vol 136 (3) ◽  
pp. 589-603 ◽  
Author(s):  
Richard W. Leu ◽  
A. L. W. F. Eddleston ◽  
John W. Hadden ◽  
Robert A. Good
Keyword(s):  
Alveolar Macrophage ◽  
Peritoneal Macrophage ◽  
Migration Inhibitory Factor ◽  
Immune Modulation ◽  
Peritoneal Macrophages ◽  
Cell Number ◽  
Inhibitory Factor ◽  
Cell Surface Receptor ◽  
Specific Cell ◽  
Surface Receptor

The initial interaction between migration inhibitory factor (MIF) and the guinea pig alveolar and peritoneal macrophage was studied. MIF-containing supernatants were generated from sensitized lymph node lymphocytes obtained from guinea pigs immunized with bovine gamma globulin in complete Freund's adjuvant. MIF-containing supernatants were markedly inhibitory for the migration of the peritoneal macrophage but had no effect on the alveolar macrophage. A linear relationship was observed between per cent inhibition of migration and serial twofold dilution of supernatant. Reexpressed in arbitrary MIF units, this relationship reflects a dose-response relationship with saturation characteristics. Pulse exposure of peritoneal macrophages to MIF resulted in adsorption of MIF onto both viable and nonviable cells with corresponding depletion of supernatant MIF. The alveolar macrophage did not adsorb MIF. Pulse adsorption of MIF onto the peritoneal macrophage is dependent on time, temperature, and cell number. Pretreatment of the cells with proteolytic enzyme prevents the adsorption of MIF while leaving migration unaffected. These observations support the existence of a specific cell surface receptor for MIF. The existence of such a receptor provides selectivity of immune modulation of macrophage populations by lymphocytes in delayed hypersensitivity reactions.

Functional characteristics of PMJ2-R macrophages

2020 ◽  
Vol 18 (4) ◽  
pp. 133-137
Author(s):  
P.M. Kozhin ◽  
◽  
A.L. Rusanov ◽  
O.O. Shoshina ◽  
N.G. Luzgina ◽  
...  
Keyword(s):  
Cell Biology ◽  
Alternative Pathway ◽  
Peritoneal Macrophages ◽  
Alternative Activation ◽  
M2 Macrophages ◽  
Phagocytic Cells ◽  
Phenotypic Properties ◽  
M1 Macrophages ◽  
Oxidized Dextran ◽  
Tnf Α

Objective. To evaluate the ability of PMJ2-R cells for classical and alternative activation and to assess the effect of oxidized dextran on the functional status of polarized cells of this line. OD is a promising lysosomotropic agent used for targeted drug delivery to phagocytic cells. Materials and methods. We analyzed ability of immortalized murine peritoneal macrophages PMJ2R (ATCC CRL2458) to classical and alternative polarization, including that upon exposure to OD. We used real-time polymerase chain reaction to assess gene expression of competing arginine pathways. The capacity of phagocytes to engulf zymosan granules was evaluated using fluorescence microscopy. Results. We observed metabolic changes in PMJ2-R cells following their classical and alternative activation; these changes were typical of M1 and M2 macrophages, respectively. M1 macrophages demonstrated most active phagocytosis, while the activity of phagocytosis in M2 macrophages increased dose-dependently upon AD exposure. OD upregulates production of proinflammatory cytokine TNF-α in intact PMJ2-R cells and M1 macrophages. Conclusion. PMJ2-R cells have the capacity to phagocytose particles, can be polarized via the classical and alternative pathway, can modulate their functional activity in response to OD (a macrophagotropic substance), and exhibit the main phenotypic properties typical of peritoneal macrophages from C57Bl/6J mice. Therefore, cells of this line can be used as model cells in the investigation of phagocytic cell biology and pathology. Key words: alternative activation, classical activation, oxidized dextran, peritoneal macrophages, phagocytosis, C57Bl/6J, PMJ2-R

Dibutyryl Cytidine and Adenosine 3':5'-Cyclic Monophosphates Inhibit A23187-Stimulated Rat Peritoneal Macrophage Leukotriene B4 Synthesis

1988 ◽  
Vol 1 (2) ◽  
pp. 109-114
Author(s):  
G. R. Elliott ◽  
A. P. M. Lauwen ◽  
I. L. Bonta
Keyword(s):  
Peritoneal Macrophage ◽  
Calcium Ionophore ◽  
Peritoneal Macrophages ◽  
Leukotriene B4 ◽  
Calcium Ionophore A23187 ◽  
Intracellular Camp ◽  
Ionophore A23187 ◽  
Eicosanoid Release ◽  
Stable Product

Dibutyryl cytidine and adenosine 3':5'-cyclic monophosphates (db-cCMP and db-cAMP respectively) inhibited the synthesis of thromboxane (TX) B2, the stable product of TXA2, and leukotriene (LT) B4 by 4-day carrageenin-elicited rat peritoneal macrophages stimulated by the calcium ionophore A23187. Incubation of macrophages with dbcAMP, at concentrations inhibiting eicosanoid release, was associated with an increase in intracellular cAMP concentrations. No such increase was seen when db-cCMP was used.

scholarly journals Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Melissa M. Bunting ◽  
Alexander M. Shadie ◽  
Rylie P. Flesher ◽  
Valentina Nikiforova ◽  
Linda Garthwaite ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Acute Exacerbation ◽  
Proinflammatory Cytokines ◽  
Alveolar Macrophages ◽  
Surface Proteins ◽  
Alternative Activation ◽  
Chronic Asthma ◽  
Activation Markers ◽  
Interleukin 33 ◽  
Enhanced Expression

We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

scholarly journals The biology of nematode- and IL4Rα-dependent murine macrophage polarization in vivo as defined by RNA-Seq and targeted lipidomics

Blood ◽  
2012 ◽  
Vol 120 (25) ◽  
pp. e93-e104 ◽  
Author(s):  
Graham D. Thomas ◽  
Dominik Rückerl ◽  
Benjamin H. Maskrey ◽  
Phillip D. Whitfield ◽  
Mark L. Blaxter ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Expression Profiles ◽  
Macrophage Polarization ◽  
Peritoneal Macrophages ◽  
Mitochondrial Metabolism ◽  
Alternative Activation ◽  
Alternatively Activated Macrophages ◽  
Transcription Start Sites

Abstract Alternatively activated macrophages (AAMφ) are a major component of the response to helminth infection; however, their functions remain poorly defined. To better understand the helminth-induced AAMφ phenotype, we performed a systems-level analysis of in vivo derived AAMφ using an established mouse model. With next-generation RNA sequencing, we characterized the transcriptomes of peritoneal macrophages from BALB/c and IL4Rα−/− mice elicited by the nematode Brugia malayi, or via intraperitoneal thioglycollate injection. We defined expression profiles of AAMφ-associated cytokines, chemokines, and their receptors, providing evidence that AAMφ contribute toward recruitment and maintenance of eosinophilia. Pathway analysis highlighted complement as a potential AAMφ-effector function. Up-regulated mitochondrial genes support in vitro evidence associating mitochondrial metabolism with alternative activation. We mapped macrophage transcription start sites, defining over-represented cis-regulatory motifs within AAMφ-associated promoters. These included the binding site for PPAR transcription factors, which maintain mitochondrial metabolism. Surprisingly PPARγ, implicated in the maintenance of AAMφ, was down-regulated on infection. PPARδ expression, however, was maintained. To explain how PPAR-mediated transcriptional activation could be maintained, we used lipidomics to quantify AAMφ-derived eicosanoids, potential PPAR ligands. We identified the PPARδ ligand PGI2 as the most abundant AAMφ-derived eicosanoid and propose a PGI2-PPARδ axis maintains AAMφ during B malayi implantation.

scholarly journals Peroxisome proliferator-activated receptor α and γ agonists differently regulate classical and alternative macrophage activation

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Erja-Leena Paukkeri ◽  
Antti Pekurinen ◽  
Eeva Moilanen
Keyword(s):  
Macrophage Activation ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Alternative Activation ◽  
Peroxisome Proliferator ◽  
Activation Markers ◽  
Peroxisome Proliferator Activated Receptor ◽  
Arginase 1 ◽  
Pparγ Agonist ◽  
Ppar Agonists

AbstractPeroxisome proliferator-activated receptor (PPAR) agonists, fibrates and thiazolidinediones, are commonly used drugs in the treatment of dyslipidemia and diabetes. Their targets, PPARα and PPARγ, have also been shown to have a role in the regulation of inflammatory responses linking metabolism and inflammation. In the present study we investigated the effects of PPAR agonists on macrophage activation. In addition to the proinflammatory classical activation, we also focused on interleukin (IL) 4 and 13 -induced alternative activation which is a significant macrophage phenotype in tissue repairing processes and in fibrosing diseases. PPARα agonists GW7647 and fenofibrate as well as PPARγ agonist GW1929 inhibited lipopolysaccharide-induced classical macrophage activation and production of the characteristic biomarkers of this phenotype, i.e. IL-6 and nitric oxide, in murine J774 macrophages. Remarkably, the PPARα agonists also inhibited IL-4 and IL-13 –induced expression of alternative activation markers arginase-1, fizz1 and mannose receptor 1 whereas the PPARγ agonist GW1929 enhanced their expression in J774 macrophages. The PPARα agonists GW7647 and fenofibrate also attenuated the production of alternative activation markers chemokine (C-C motif) ligand 13 and plateletderived growth factor in human THP-1 macrophages. The present findings show that PPARα and PPARγ agonists differently regulate classical and alternative macrophage phenotypes. Furthermore, PPARα activation was introduced as a novel concept to down-regulate alternative macrophage activation indicating that PPARα agonists have therapeutic potential in conditions associated with aberrant alternative macrophage activation such as fibrosing diseases.

scholarly journals Pelvic pain correlates with peritoneal macrophage abundance not endometriosis

2021 ◽  
Vol 2 (1) ◽  
pp. 47-57
Author(s):  
Douglas A Gibson ◽  
Frances Collins ◽  
Bianca De Leo ◽  
Andrew W Horne ◽  
Philippa T K Saunders
Keyword(s):  
Pain Score ◽  
Peritoneal Macrophage ◽  
Pelvic Pain ◽  
Immune Cells ◽  
Peritoneal Fluid ◽  
Peritoneal Macrophages ◽  
The Body ◽  
Disease Stage ◽  
Pain Scores ◽  
Pain Symptoms

Endometriosis is a chronic neuroinflammatory pain condition affecting ~180 million women worldwide. Surgical removal or hormonal suppression of endometriosis lesions only relieves pain symptoms in some women and symptomatic relapse following treatment is common. Identifying factors that contribute to pain is key to developing new therapies. We collected peritoneal fluid samples and clinical data from a cohort of women receiving diagnostic laparoscopy for suspected endometriosis (n = 52). Peritoneal fluid immune cells were analysed by flow cytometry and data compared with pain scores determined using the pain domain of the Endometriosis Health Profile Questionnaire (EHP-30) in order to investigate the association between peritoneal immune cells and pain symptoms. Pain scores were not different between women with or without endometriosis, nor did they differ according to disease stage; consistent with a poor association between disease presentation and pain symptoms. However, linear regression and correlation analysis demonstrated that peritoneal macrophage abundance correlated with the severity of pelvic pain. CD14high peritoneal macrophages negatively correlated with pain scores whereas CD14low peritoneal macrophages were positively correlated, independent of diagnostic outcome at laparoscopy. Stratification by pain subtype, rather than endometriosis diagnosis, resulted in the most robust correlation between pain and macrophage adundance. Pain score strongly correlated with CD14high (P = 0.007) and CD14low (P = 0.008) macrophages in patients with non-menstrual pain and also in patients who reported dysmennorhea (CD14high P = 0.021, CD14low P = 0.019) or dysparunia (CD14high P = 0.027, CD14low P = 0.031). These results provide new insight into the association between peritoneal macrophages and pelvic pain which may aid the identification of future therapeutic targets. Lay summary Endometriosis is a common condition where cells similar to those that line the womb are found elsewhere in the body. It is associated with inflammation and pain in the pelvis and affects ~180 million women worldwide. Current treatments are not effective for all patients and we, therefore, need to understand what causes pain in order to develop new treatments. We investigated the types of immune cells present within the pelvis of women undergoing investigation for suspected endometriosis. Disease diagnosis and stage (I–IV) was recorded along with pain score determined by questionnaire. We characterised the immune cells present and compared them to disease stage and pain score. We found that pelvic pain was linked to the abundance of immune cells but, surprisingly, not to disease stage. These findings suggest that immune cells are closely associated with pain severity in endometriosis and may be good targets for future endometriosis treatments.

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