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 Human and Mouse Macrophages Collaborate with Neutrophils To Kill Larval Strongyloides stercoralis

2013 ◽  
Vol 81 (9) ◽  
pp. 3346-3355 ◽  
Author(s):  
Sandra Bonne-Année ◽  
Laura A. Kerepesi ◽  
Jessica A. Hess ◽  
Amy E. O'Connell ◽  
James B. Lok ◽  
...  
Keyword(s):  
Strongyloides Stercoralis ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Parasitic Helminths ◽  
Time Period ◽  
Mouse Macrophages ◽  
Classically Activated Macrophages ◽  
Human And Mouse

ABSTRACTMacrophages are multifunctional cells that are active in TH1- and TH2-mediated responses. In this study, we demonstrate that human and mouse macrophages collaborate with neutrophils and complement to kill the parasiteStrongyloides stercoralis in vitro. Infection of mice with worms resulted in the induction of alternatively activated macrophages (AAMϕ) within the peritoneal cavity. These cells killed the wormsin vivoand collaborated with neutrophils and complement during thein vitrokilling process. AAMϕ generatedin vitrokilled larvae more rapidly than naive macrophages, which killed larvae after a longer time period. In contrast, classically activated macrophages were unable to kill larvae eitherin vitroorin vivo. This study adds macrophages to the armamentarium of immune components that function in elimination of parasitic helminths and demonstrate a novel function by which AAMϕ control large extracellular parasites.

scholarly journals Interdependence between Chromogranin-A, Alternatively Activated Macrophages, Tight Junction Proteins and the Epithelial Functions. A Human and In-Vivo/In-Vitro Descriptive Study

2020 ◽  
Vol 21 (21) ◽  
pp. 7976
Author(s):  
Nour Eissa ◽  
Hayam Hussein ◽  
Diane M. Tshikudi ◽  
Geoffrey N. Hendy ◽  
Charles N. Bernstein ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Chromogranin A ◽  
Intestinal Inflammation ◽  
Collagen Deposition ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Alternatively Activated

Background: Ulcerative colitis (UC) is characterized by altered chromogranin-A (CHGA), alternatively activated macrophages (M2) and intestinal epithelial cells (IECs). We previously demonstrated that CHGA is implicated in colitis progression by regulating the macrophages. Here, we investigated the interplay between CHGA, M2, tight junctions (TJ) and IECs in an inflammatory environment. Methods: Correlations between CHGA mRNA expression of and TJ proteins mRNA expressions of (Occludin [OCLN], zonula occludens-1 [ZO1], Claudin-1 [CLDN1]), epithelial associated cytokines (interleukin [IL]-8, IL-18), and collagen (COL1A2) were determined in human colonic mucosal biopsies isolated from active UC and healthy patients. Acute UC-like colitis (5% dextran sulphate sodium [DSS], five days) was induced in Chga-C57BL/6-deficient (Chga−/−) and wild type (Chga+/+) mice. Col1a2 TJ proteins, Il-18 mRNA expression and collagen deposition were determined in whole colonic sections. Naïve Chga−/− and Chga+/+ peritoneal macrophages were isolated and exposed six hours to IL-4/IL-13 (20 ng/mL) to promote M2 and generate M2-conditioned supernatant. Caco-2 epithelial cells were cultured in the presence of Chga−/− and Chga+/+ non- or M2-conditioned supernatant for 24 h then exposed to 5% DSS for 24 h, and their functional properties were assessed. Results: In humans, CHGA mRNA correlated positively with COL1A2, IL-8 and IL-18, and negatively with TJ proteins mRNA markers. In the experimental model, the deletion of Chga reduced IL-18 mRNA and its release, COL1A2 mRNA and colonic collagen deposition, and maintained colonic TJ proteins. Chga−/− M2-conditioned supernatant protected caco-2 cells from DSS and oxidative stress injuries by improving caco-2 cells functions (proliferation, viability, wound healing) and by decreasing the release of IL-8 and IL-18 and by maintaining the levels of TJ proteins, and when compared with Chga+/+ M2-conditioned supernatant. Conclusions: CHGA contributes to the development of intestinal inflammation through the regulation of M2 and epithelial cells. Targeting CHGA may lead to novel biomarkers and therapeutic strategies in UC.

scholarly journals Alternatively Activated Macrophages in Types 1 and 2 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Arlett Espinoza-Jiménez ◽  
Alberto N. Peón ◽  
Luis I. Terrazas
Keyword(s):  
Type 1 Diabetes ◽  
Proinflammatory Cytokines ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Advantages And Disadvantages ◽  
Classically Activated Macrophages ◽  
Macrophage Populations ◽  
Alternatively Activated ◽  
Classically Activated

Macrophages are innate immune cells derived from monocytes, which, in turn, arise from myeloid precursor cells in the bone marrow. Macrophages have many important roles in the innate and adaptive immune response, as well as in tissue homeostasis. Two major populations have been defined: The classically activated macrophages that respond to intracellular pathogens by secreting proinflammatory cytokines and reactive oxygen species and alternatively activated macrophages which are induced during Th2 responses displaying anti-inflammatory activities. Both macrophage populations are central players in diabetes, the first one triggering inflammatory responses which initiates insulitis and pancreaticβcell death during type 1 diabetes, whereas the second population decreases hyperglycemia, insulitis, and inflammation in the pancreas, thereby negatively regulate type 1 diabetes. Obesity is an important factor in the development of type 2 diabetes; classically activated macrophages are a dominant cell population involved in the establishment of the inflammatory profile, insulin resistance, and activation of inflammatory signals during the development and progression of this disease. In contrast, alternatively activated macrophages regulate the release of proinflammatory cytokines, attenuating adipose tissue inflammation. Here, we review the advantages and disadvantages of these two macrophage populations with regard to their roles in types 1 and 2 diabetes.

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 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.

Mesenchymal Stem Cells Convert Human Macrophages to a Novel Type of Alternatively Activated Macrophages.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3632-3632 ◽  
Author(s):  
Jaehyup Kim ◽  
Peiman Hematti
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Surface ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Tnf Α ◽  
Low Levels ◽  
Alternatively Activated

Abstract Abstract 3632 Poster Board III-568 Mesenchymal stem cells (MSCs) are capable of modulating the immune system through interaction with a wide range of immune cells. This study investigates the hypothesis that interaction of MSCs with macrophages could play a significant role in their anti-inflammatory/immune modulatory effects. All studies were approved by IRB of University of Wisconsin School of Medicine and Public Health. MSCs were culture expanded from discarded bone marrow filters after bone marrow harvest from normal healthy sibling HLA-matched donors. We used passages -35 for our experiments. Ex vivo culture expanded MSCs were characterized by their cell surface phenotype (positive for MSC markers: CD29, CD44, CD73, CD90, and CD105; and negative for hematopoietic markers: CD31, CD34, and CD45), and their differentiation potential into bone, fat and cartilage. Monocytes were isolated from peripheral blood mononuclear cell fraction of healthy donors using CD14+ Miltenyi magnetic bead cell separation method. We cultured human CD14+ monocytes for seven days without any added cytokines to generate macrophages, and then co-cultured them for three more days with culture-expanded MSCs. We used cell surface antigen expression and intracellular cytokine expression patterns to study the immunophenotype of macrophages at the end of this co-culture period, and phagocytic assays to investigate their functional activity in vitro. Macrophages co-cultured with MSCs consistently showed high level expression of CD206, a marker of alternatively activated macrophages, in addition to being positive fro CD14 marker. Using CD1a and CD209 staining we did not detect presence of any dendritic cells either at the end of seven days culture of monocyte-derived macrophages or at the end of co-culture period. Furthermore, macrophages that were co-cultured with MSCs expressed high levels of IL-10 and low levels of IL-12, as determined by intracellular staining, typical of alternatively activated macrophages. However, macrophages co-cultured with MSCs also expressed high levels of IL-6 and low levels of TNF-α, compared to controls. Functionally, macrophages co-cultured with MSCs showed a higher level of phagocytic activity using Alexa 488-conjugated E. coli phagocytic assay. In summary we describe a novel type of human macrophage generated in vitro after co-culture with MSCs that assume an immunophenotype defined as IL-10 high, IL-12 low, IL-6 high and TNF-α low secreting cells. These MSC-educated macrophages may be a unique and novel type of alternatively activated macrophages with potentially significant role in tissue repair. Disclosures: No relevant conflicts of interest to declare.

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