scholarly journals Alternatively activated macrophages exhibit an anticalcifying activity dependent on extracellular ATP/pyrophosphate metabolism

2016 ◽  
Vol 310 (10) ◽  
pp. C788-C799 ◽  
Author(s):  
Ricardo Villa-Bellosta ◽  
Magda R. Hamczyk ◽  
Vicente Andrés
Keyword(s):  
Extracellular Atp ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Atherosclerotic Lesions ◽  
Nucleotide Pyrophosphatase ◽  
Forced Hydrolysis ◽  
Classically Activated Macrophages ◽  
Underlying Mechanisms ◽  
Activity Dependent ◽  
Alternatively Activated

Calcium-phosphate deposition (CPD) in atherosclerotic lesions, which begins in middle age and increases with aging, is a major independent predictor of future cardiovascular disease morbi-mortality. Remodeling of atherosclerotic vessels during aging is regulated in part by intimal macrophages, which can polarize to phenotypically distinct populations with distinct functions. This study tested the hypothesis that classically activated macrophages (M1φs) and alternatively activated macrophages (M2φs) differently affect vascular smooth muscle cell (VSMC) calcification and investigated the underlying mechanisms. We analyzed mouse VSMC-macrophage cocultures using a transwell system. Coculture of VSMCs with M2φs significantly reduced CPD, but coculture with M1φs had no effect. The anticalcific effect of M2φs was associated with elevated amounts of extracellular ATP and pyrophosphate (PPi), two potent inhibitors of CPD, and was lost upon forced hydrolysis of these metabolites. In M2φs and VSMC-M2φs cocultures, analysis of the ectoenzymes that regulate extracellular ATP/PPi metabolism revealed increased mRNA expression and activity of ectoenzyme nucleotide pyrophosphatase/phosphodiesterase-1, which synthesizes PPi from ATP, without changes in tissue-nonspecific alkaline phosphatase, which hydrolyzes PPi. In conclusion, increased accumulation of extracellular ATP and PPi by alternatively activated mouse M2φs inhibits CPD. These results reveal novel mechanisms underlying macrophage-dependent control of intimal calcification.

scholarly journals Macrophages, Meta-Inflammation, and Immuno-Metabolism

2011 ◽  
Vol 11 ◽  
pp. 2509-2529 ◽  
Author(s):  
Haim Shapiro ◽  
Aviv Lutaty ◽  
Amiram Ariel
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Extracellular Signals ◽  
Macrophage Phenotypes ◽  
Classically Activated Macrophages ◽  
Underlying Mechanisms ◽  
Alternatively Activated ◽  
Classically Activated

Current research depicts specific modes of immunity and energy metabolism as being interrelated at the molecular, cellular, organ and organism level. Hence, whereas M2 (alternatively-activated) macrophages dominate insulin-sensitive adipose tissue in the lean, M1-skewed (classically-activated) macrophages accumulate in parallel to adiposity in the obese, and promote inflammation and insulin resistance, that is, meta-inflammation. The latest frontier of immuno-metabolism explores the coregulation of energy metabolism and immune function within hematopoietic cells. M1-skewed macrophages are sustained in edematous, hypoxic tissues by anaerobic glycolysis, whereas mitochondrial biogenesis and respiration dominates in M2 cells. We review the underlying mechanisms and the consequences of the transition from M2 to M1 predominance in adipose tissue, as well as the extracellular signals and transcription factors that control macrophage phenotypes and impose distinct metabolic modes.

scholarly journals FIZZ1 and Ym as Tools to Discriminate between Differentially Activated Macrophages

2002 ◽  
Vol 9 (3) ◽  
pp. 151-159 ◽  
Author(s):  
Geert Raes ◽  
Wim Noël ◽  
Alain Beschin ◽  
Lea Brys ◽  
Patrick de Baetselier ◽  
...  
Keyword(s):  
Mouse Strains ◽  
Molecular Characteristics ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Different Populations ◽  
Classically Activated Macrophages ◽  
Macrophage Populations ◽  
Alternatively Activated

Although it is well-established that macrophages can occur in distinct activation states, the molecular characteristics of differentially activated macrophages, and particularly those of alternatively activated macrophages (aaMφ), are still poorly unraveled. Recently, we demonstrated that the expression of FIZZ1 and Ym is induced in aaMφ as compared with classically activated macrophages (caMφ), elicitedin vitroor developedin vivoduring infection withTrypanosoma brucei brucei. In the present study, we analyzed the expression of FIZZ1 and Ym in caMφ and aaMφ elicited duringTrypanosoma congolenseinfection and show that the use of FIZZ1 and Ym for the identification of aaMφ is not limited toT. b. bruceiinfection and is independent of the organ sources from which macrophages are obtained. We also demonstrate that FIZZ1 can be used to discriminate between different populations of aaMφ. Furthermore, we studied the effects of various stimuli, and combinations thereof, on the expression of FIZZ1 and Ym in macrophages from different mouse strains and demonstrate that regulation of the expression of FIZZ1 and Ym in macrophages is not dependent on the mouse strain. Finally, we show that these genes can be used to monitor the macrophage activation status without the need to obtain pure macrophage populations.

scholarly journals Adenylate Kinase 4 Promotes Inflammatory Gene Expression via Hif1α and AMPK in Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-Yao Chin ◽  
Chi-Ying He ◽  
Tsun Wai Chow ◽  
Qi-You Yu ◽  
Liang-Chuan Lai ◽  
...  
Keyword(s):  
Adenylate Kinase ◽  
Activated Macrophages ◽  
Rna Seq ◽  
M1 Macrophages ◽  
Alternatively Activated Macrophages ◽  
Atp Production ◽  
Cell Functions ◽  
Inflammatory Processes ◽  
Classically Activated Macrophages ◽  
Alternatively Activated

Macrophages comprise the front line of defense against various pathogens. Classically activated macrophages (M1), induced by IFN-γ and LPS, highly express inflammatory cytokines and contribute to inflammatory processes. By contrast, alternatively activated macrophages (M2) are induced by IL-4 and IL-13, produce IL-10, and display anti-inflammatory activity. Adenylate kinase 4 (Ak4), an enzyme that transfers phosphate group among ATP/GTP, AMP, and ADP, is a key modulator of ATP and maintains the homeostasis of cellular nucleotides which is essential for cell functions. However, its role in regulating the function of macrophages is not fully understood. Here we report that Ak4 expression is induced in M1 but not M2 macrophages. Suppressing the expression of Ak4 in M1 macrophages with shRNA or siRNA enhances ATP production and decreases ROS production, bactericidal ability and glycolysis in M1 cells. Moreover, Ak4 regulates the expression of inflammation genes, including Il1b, Il6, Tnfa, Nos2, Nox2, and Hif1a, in M1 macrophages. We further demonstrate that Ak4 inhibits the activation of AMPK and forms a positive feedback loop with Hif1α to promote the expression of inflammation-related genes in M1 cells. Furthermore, RNA-seq analysis demonstrates that Ak4 also regulates other biological processes in addition to the expression of inflammation-related genes in M1 cells. Interestingly, Ak4 does not regulate M1/M2 polarization. Taken together, our study uncovers a potential mechanism linking energy consumption and inflammation in macrophages.

scholarly journals Group-2 innate lymphoid cell-dependent regulation of tissue neutrophil migration by alternatively activated macrophage-secreted Ear11

2020 ◽  
Vol 14 (1) ◽  
pp. 26-37 ◽  
Author(s):  
Veera Panova ◽  
Mayuri Gogoi ◽  
Noe Rodriguez-Rodriguez ◽  
Meera Sivasubramaniam ◽  
Helen E. Jolin ◽  
...  
Keyword(s):  
Neutrophil Migration ◽  
Neutrophil Infiltration ◽  
Rnase A ◽  
Activated Macrophages ◽  
Mucus Production ◽  
Alternatively Activated Macrophages ◽  
Group 2 ◽  
Classically Activated Macrophages ◽  
Alternatively Activated

AbstractType-2 immunity is characterised by interleukin (IL)-4, IL-5 and IL-13, eosinophilia, mucus production, IgE, and alternatively activated macrophages (AAM). However, despite the lack of neutrophil chemoattractants such as CXCL1, neutrophils, a feature of type-1 immunity, are observed in type-2 responses. Consequently, alternative mechanisms must exist to ensure that neutrophils can contribute to type-2 immune reactions without escalation of deleterious inflammation. We now demonstrate that type-2 immune-associated neutrophil infiltration is regulated by the mouse RNase A homologue, eosinophil-associated ribonuclease 11 (Ear11), which is secreted by AAM downstream of IL-25-stimulated ILC2. Transgenic overexpression of Ear11 resulted in tissue neutrophilia, whereas Ear11-deficient mice have fewer resting tissue neutrophils, whilst other type-2 immune responses are not impaired. Notably, administration of recombinant mouse Ear11 increases neutrophil motility and recruitment. Thus, Ear11 helps maintain tissue neutrophils at homoeostasis and during type-2 reactions when chemokine-producing classically activated macrophages are infrequently elicited.

scholarly journals Taenia crassiceps Antigens Control Experimental Type 1 Diabetes by Inducing Alternatively Activated Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Arlett Espinoza-Jiménez ◽  
Roberto De Haro ◽  
Luis I. Terrazas
Keyword(s):  
Type 1 Diabetes ◽  
Suppressor Cells ◽  
Activated Macrophages ◽  
Taenia Crassiceps ◽  
Alternatively Activated Macrophages ◽  
Helminth Infections ◽  
Experimental Type ◽  
Classically Activated Macrophages ◽  
Alternatively Activated

Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of the pancreatic β-cells, causing inability to produce insulin. Proinflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-γ, IL-12, IL-17, and NO can be released by CD4 and CD8+ lymphocytes as well as by classically activated macrophages (CAMϕs), which are important in the development of T1D. Helminth infections have been shown to prevent T1D, mainly through Th2-biased responses and increased recruitment of regulatory cell populations. Previously, we have shown that Taenia crassiceps infection in mice significantly reduces hyperglycemia, insulitis, and the incidence of T1D. In this study, we determined whether T. crassiceps-derived products such as soluble (TcS) or excreted/secreted (TcES) antigens might have a beneficial influence on the development of experimental T1D. Treatment with different doses before or after induction of T1D was analyzed. Mice that were pretreated with TcS were unable to develop T1D, whereas those receiving TcES early after T1D induction displayed significantly reduced insulitis and hyperglycemia along with increased recruitment of alternatively activated macrophages (AAMϕs) and myeloid-derived suppressor cells (MDSCs). Finally, we examined the modulatory role of AAMϕs on T1D by depleting macrophages with clodronate-loaded liposomes, demonstrating that AAMϕs are key cells in T1D regulation.

scholarly journals Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew Stephens ◽  
Shan Liao ◽  
Pierre-Yves von der Weid
Keyword(s):  
Bacterial Species ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
E Coli ◽  
Activation Of Transcription ◽  
Classically Activated Macrophages ◽  
Species Specific ◽  
Inducible Genes ◽  
Alternatively Activated ◽  
Classically Activated

AbstractTLR4 location, and bacterial species-derived lipopolysaccharides, play a significant role in the downstream activation of transcription factors, accessory molecules, and products. Here, this is demonstrated through the use of classically-activated and alternatively-activated macrophages. We show that, when polarized, human macrophages differentially express and localize TLR4, resulting in biased recognition and subsequent signalling of LPS derived from Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica. Analysis of activation demonstrated that in classically activated macrophages, P. aeruginosa signals from the plasma membrane via TLR4 to p65 dependent on TAK1 and TBK1 signalling. E. coli signals dependent or independent of the endosome, utilizing both TAK1- and TBK1-signalling to induce P65 and IRF3 inducible genes and cytokines. S. enterica however, only induces P65 and IRF3 phosphorylation through signalling via the endosome. This finding outlines clear signalling mechanisms by which innate immune cells, such as macrophages, can distinguish between bacterial species and initiate specialized responses through TLR4.

Sign in / Sign up

Export Citation Format

Share Document