Fingerprint Dive into the research topics of Selenoproteome Identification in Inflamed Murine Primary Bone Marrow-Derived Macrophages by Nano-LC Orbitrap Fusion Tribrid Mass Spectrometry. Together they form a unique fingerprint. ...

The hallmark of the human atherosclerotic plaque is the presence of lipid-laden macrophages, or foam cells. However, many macrophage subsets are found within atherosclerotic lesions and it is not well understood how monocytes differentiate into these subsets. We focused on characterizing macrophages derived in vitro from human peripheral blood monocytes treated with IL-15, IL-4 or IL-10. We show these macrophages to have differing phenotypes: CD209+CD64+, CD209+CD23+, or CD209+CD163+ for macrophages derived from IL-15, IL-4, or IL-10 respectively. To characterize the macrophage subsets ability to become foam cells we measured their uptake of fluorescently-labeled oxidized LDL (oxLDL). IL-10 derived macrophages had the greatest amount of oxLDL uptake. We then investigated the mechanism of uptake and found that fucoidan, a class-A scavenger receptor competitor, significantly inhibited uptake of oxLDL in IL-10 cells. On the other hand a blocking antibody against the class B scavenger receptor, ...

Toll-like receptors (TLRs) and macrophages play an important role in rheumatoid arthritis (RA). Currently, it is not clear whether inflammatory M1 or anti-inflammatory M2 predominate among the resident macrophages in the synovium. In the present study, we set out to investigate the impact of TLR stimulation on monocyte-derived M1 and M2 macrophage function and phenotype by mimicking the exposure to abundant TLR agonists as occurs in the context of RA. The response of macrophage subsets to TLR2 and TLR4 activation was evaluated on cluster of differentiation (CD) marker profile; cytokine secretion; gene expression; and NF-κB, interferon regulatory factors 3 and 7 (IRF3/7), and mitogen-activated protein kinase (MAPK) activation. Human monocytes were isolated from peripheral blood of healthy individuals and patients with RA and differentiated into M1-like and M2-like macrophages by granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively.

TY - JOUR. T1 - BCL6 suppresses RhoA activity to alter macrophage morphology and motility. AU - Pixley, Fiona J.. AU - Xiong, Ying. AU - Yu, Raymond Yick Loi. AU - Sahai, Erik A.. AU - Stanley, E. Richard. AU - Ye, B. Hilda. PY - 2005/5/1. Y1 - 2005/5/1. N2 - BCL6 is a potent transcriptional repressor that plays important roles in germinal center formation, T helper cell differentiation and lymphomagenesis and regulates expression of several chemokine genes in macrophages. In a further investigation of its role in macrophages, we show that BCL6 inactivation in primary bone marrow-derived macrophages leads to decreased polarization, motility and cell spreading accompanied by an increase in peripheral focal complexes, anchored F-actin bundles and cortical F-actin density. These changes were associated with excess RhoA activation. C3 transferase inhibition of RhoA activity reverted the adhesion structure phenotype, which was not affected by Rho kinase inhibitors, suggesting that other downstream ...

Chemotaxis assays are an invaluable tool for studying the biological activity of inflammatory mediators such as CC chemokines, which have been implicated in a wide range of chronic inflammatory diseases. Conventional chemotaxis systems such as the modified Boyden chamber are limited in terms of the data captured given that the assays are analysed at a single time-point. We report the optimisation and validation of a label-free, real-time cell migration assay based on electrical cell impedance to measure chemotaxis of different primary murine macrophage populations in response to a range of CC chemokines and other chemoattractant signalling molecules. We clearly demonstrate key differences in the migratory behavior of different murine macrophage populations and show that this dynamic system measures true macrophage chemotaxis rather than chemokinesis or fugetaxis. We highlight an absolute requirement for Gαi signaling and actin cytoskeletal rearrangement as demonstrated by Pertussis toxin and

Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes. ...

Gaucher disease is caused by an inherited deficiency of glucocerebrosidase that manifests with storage of glycolipids in lysosomes, particularly in macrophages. Available cell lines modeling Gaucher disease do not demonstrate lysosomal storage of glycolipids; therefore, we set out to develop two macrophage models of Gaucher disease that exhibit appropriate substrate accumulation. We used these cellular models both to investigate altered macrophage biology in Gaucher disease and to evaluate candidate drugs for its treatment. We generated and characterized monocyte-derived macrophages from 20 patients carrying different Gaucher disease mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived macrophages from five fibroblast lines taken from patients with type 1 or type 2 Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed reduced glucocerebrosidase activity and increased storage of glucocerebroside and glucosylsphingosine in lysosomes. These ...

Infections caused by organisms of the Mycobacterium avium complex occur in approximately 50 to 60% of patients with AIDS. M. avium is an intracellular pathogen that survives and multiplies within mononuclear phagocytes. In this study, we investigated the uptake of M. avium grown within macrophages (intracellular growth M. avium [IG]) by a second macrophage compared with M. avium cultured in broth (extracellular growth M. avium [EG]). The results showed that IG was six- to eightfold more efficient than EG in entering macrophages. In addition, while an anti-CR3 antibody was able to inhibit approximately 60% of EG uptake by macrophages, it failed to inhibit the entry of IG. In contrast to EG, IG uptake into macrophages was significantly inhibited in the presence of anti-beta1-integrin and anti-transferrin receptor antibodies. Entry into macrophages by alternate receptors was associated with resistance to tumor necrosis factor alpha (TNF-alpha) stimulation. While stimulation with TNF-alpha resulted ...

TY - JOUR. T1 - Distinct macrophage phenotypes in allergic and nonallergic lung inflammation. AU - Robbe, Patricia. AU - Draijer, Christina. AU - Borg, Thiago. AU - Luinge, Marjan. AU - Timens, Wim AU - Wouters, IM. AU - Melgert, Barbro. AU - Hylkema, MN. PY - 2015/2/15. Y1 - 2015/2/15. N2 - Chronic exposure to farm environments is a risk factor for nonallergic lung disease. In contrast to allergic asthma, in which type 2 helper T cell (Th2) activation is dominant, exposure to farm dust extracts (FDE) induces Th1/Th17 lung inflammation, associated with neutrophil infiltration. Macrophage influx is a common feature of both types of lung inflammation, allergic and nonallergic. However, macrophage functions and phenotypes may vary according to their polarized state, which is dependent on the cytokine environment. In this study, we aimed to characterize and quantify the lung macrophage populations in two established murine models of allergic and nonallergic lung inflammation by means of ...

The heterogeneity of myeloid-derived cells is a well-known phenomenon in cancer (46-48), wound healing (5, 7), and was recently also described in sterile CNS trauma (10, 11). In this study, such heterogeneity was demonstrated in an autoimmune pathological condition within the CNS, autoimmune uveitis. This diversity was manifested in this study by the presence of resident microglia, as well as infiltrating monocyte-derived macrophages in the uveitic retina, the latter being recruited only upon disease induction. Moreover, within the infiltrating macrophage population, we identified different phenotypic subsets, the frequencies of which changed along the disease course, and which appeared to have distinct functional effects, contributing differentially to disease induction and resolution. The fact that specific depletion of the infiltrating macrophages, when performed at the resolution phase, resulted in impaired EAU resolution indicates that monocyte-derived macrophages performed a role that ...

It is widely known that macrophages can be activated to kill tumor cells. It is also known that tumor-infiltrating macrophages can be immunosuppressed. The mechanisms of both tumor killing by activated macrophages and tumor-induced macrophage suppression are not entirely clear. To better understand the mechanisms that macrophages use to kill tumor cells, a murine macrophage cell line, RAW264.7, was fixed with paraformaldehyde, subsequently stimulated with lipopolysaccharide (LPS) and co-cultured with tumor cells. Macrophage activity was assessed by nitric oxide (NO) production and tumor cell growth inhibition in the 3H-thymidine incorporation assay. It was found that fixed macrophages were still able to suppress the proliferation of tumor cells while the production of NO was abrogated. Additionally, a model of tumor-induced suppression of macrophages was developed by co-culturing them with tumor cell conditioned media before adding LPS. Inhibition of macrophage activity by tumor cell products ...

Background: The immune response mediated by tumour-associated macrophages (TAMs) is vital in tumour progression in many cancers. Fibrinogen-like protein 2 (FGL2) is a critical immunosuppressive factor that regulates the tumour microenvironment. However, no study has yet report...

In this study we immunophenotypically differentiate subpopulations of brain macrophages into perivascular macrophages and parenchymal microglia and demonstrate that perivascular macrophages are the major cell productively infected by SIV in the CNS of macaques. Preferential infection of perivascular macrophages in the CNS may account for several important observations concerning infection of the CNS, viral dynamics in the CNS, and the role of the CNS as a viral sanctuary or reservoir.. Although it has not been directly demonstrated, it is generally assumed that lentiviruses enter the CNS by the traffic of infected monocyte/macrophages (64). Our data showing that perivascular macrophages are the major cell type, infected in the brain, support this hypothesis. Studies in chimeric rodents and humans receiving bone marrow indicate that perivascular macrophages are continuously replaced from the circulation (15)(16)(17)(43). The immunophenotype described for perivascular macrophages, ...

Inflammation is associated with macrophage activation, and this process has been shown to occur during atherogenesis. Macrophages (J774A.1) that were activated with either lipopolysaccharide (LPS), zymosan, or phorbol ester demonstrated a 30-35% increased uptake and degradation of low density lipoprotein (LDL) in comparison with nonactivated cells. This phenomenon was also shown for LDL cellular binding, and it resulted in macrophage cholesterol accumulation, as evidenced by cholesterol mass determination and flow cell cytometric analysis. Enhanced uptake of LDL was also obtained with two other types of macrophages: mouse peritoneal macrophages and human monocyte-derived macrophages. In LPS-stimulated macrophages, high density lipoprotein-mediated cholesterol efflux was not different from that shown in nonstimulated cells. Cellular cholesterol synthesis, however, was increased by 25% in the activated macrophages. Macrophage activation, measured as cellular procoagulant activity, was higher in ...

TY - JOUR. T1 - Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype. AU - Boehler, R. M.. AU - Kuo, R.. AU - Shin, S.. AU - Goodman, A. G.. AU - Pilecki, M. A.. AU - Leonard, J. N.. AU - Shea, L. D.. PY - 2014/6. Y1 - 2014/6. N2 - Gene delivery from biomaterials can create an environment that promotes and guides tissue formation. However, the immune response induced upon biomaterial implantation can be detrimental to tissue regeneration. Macrophages play a central role in mediating early phases of this response, and functional polarization of macrophages towards M1 (inflammatory) or M2 (anti-inflammatory) phenotypes may bias the local immune state at the implant site. Since gene delivery from biomaterial scaffolds can confer transgene expression in macrophages in vivo, we investigated whether transduction of macrophages with an IL-10 encoding lentivirus can (1) induce macrophage polarization toward an M2 phenotype even in an ...

Macrophages are mononuclear phagocytes derived from haematopoietic progenitors that are widely distributed throughout the body. These cells participate in both innate and adaptive immune responses and lie central to the processes of inflammation, development, and homeostasis. Macrophage physiology varies depending on the environment in which they reside and they exhibit rapid functional adaption in response to external stimuli. To study macrophages in vitro, cells are typically cultured ex vivo from the peritoneum or alveoli, or differentiated from myeloid bone marrow progenitor cells to form bone marrow-derived macrophages (BMDMs). BMDMs represent an efficient and cost-effective means of studying macrophage biology. However, the inherent sensitivity of macrophages to biochemical stimuli (such as cytokines, metabolic intermediates, and RNS/ROS) makes it imperative to control experimental conditions rigorously. Therefore, the aim of this study was to establish an optimised and standardised method for the

Axol iPSC-Derived Macrophages are derived from iPSCs that have undergone an intermediate differentiation to monocytes prior to directed terminal differentiation to macrophages. This provides a highly pure and consistently reproducible population of macrophages. To support the growth and maintenance of Axol iPSC-Derived Macrophages, we offer a chemically defined, serum-free, fully optimized Macrophage Maintenance Medium.. One of the key functions of macrophages is to clean up! More specifically, by engulfing and destroying foreign substances, cell debris and microbes. Our iPSC-Derived Macrophages are highly phagocytic and express the ionized calcium-binding adapter molecule 1 (IBA1), which is typically expressed by macrophages upon activation.. When recruited to the site of injury and infection macrophages have the ability to differentiate to specific macrophage subtypes dependent on their location within the body. Within the lungs, pulmonary macrophages are a good example of tissue-specific ...

Macrophages are usually found in tumor infiltrates where they exert cytostatic/cytotoxic activities against tumor cells. The tumoricidal activity is enhanced by activation of macrophages with bacterial products or cytokines (1,2). Recently nitric oxide (NO) has been indicated as a critical effector molecule for macrophage anti-tumor activity (3,4). Macrophages can be induced to release NO upon stimulation with a variety of stimuli such as bacterial products or cytokines (3,5). More recently it has been reported that mycoplasma-treated macrophages release large amounts of NO (6).. YAC-1 tumor cells have been classically used as targets for natural killer (NK) cells. Resident macrophages do not present anti-YAC-1 activity, but lymphokine-activated macrophages are able to kill YAC-1 cells (7). The mechanism by which lymphokine-activated macrophages kill YAC-1 cells remains unsettled.. Based on these observations, we asked whether mycoplasma-infected YAC-1 tumor cells could stimulate macrophages to ...

TY - JOUR. T1 - Effect of SXWS/WSXWS peptides on chemotaxis and adhesion of the macrophage-like cell line J774. AU - Szabõ, Rita. AU - Láng, Orsolya. AU - Láng, Júlia. AU - Illyés, Eszter. AU - Köhidai, Lászlõ. AU - Hudecz, Ferenc. PY - 2015/4. Y1 - 2015/4. N2 - WSXWS motif is a conserved amino acid sequence that is present in type I cytokine receptors. This motif that can be found both in the ligand binding chains and signal transducer molecule of the receptors with different amino acids at the position X plays a role in the receptor folding, ligand binding and signal transduction as well. Structural analysis proved that WSEWS motif of IL-6R is located in a highly accessible location in the protein. Structural properties and chemotaxis of a tetrapeptide library with SXWS sequence, where X was the 19 proteinogenic amino acids except cystein were systematically studied earlier. It has been proved that C-terminal amidation and the identity of amino acid X had a pronounced influence on ...

Macrophage recognition of Candida albicans (C. albicans) is facilitated by pattern recognition receptors that interact with the fungal pathogen associated molecular patterns (PAMPs). Dectin-1 is the major macrophage receptor that is known to recognize fungal Beta-glucans leading to induction of various immune responses. This receptor is also known to be required for in vivo protection against C. albicans (Taylor et al., 2007). We recently showed that the Dectin-1 mediated protection in vivo is strain-dependent, and that C. albicans can adapt to modulate immune recognition by Dectin-1 (Marakalala et al., 2013). In vitro analysis, however, showed a Dectin-1-dependent and pro-inflammatory responses against all strains tested. This protocol describes in detail the in vitro analysis used in the paper. In particular, methods involved in fluorescent labeling of live C. albicans, quantification of macrophage binding of the pathogen, and pro-inflammatory responses to yeast and hyphal forms of the fungi are

Macrophages display remarkable plasticity, with the ability to undergo dynamic transition between different functional phenotypes.63,64 Macrophages activated by TLR ligands and IFN-γ are called M1 macrophages (also referred to as classically activated macrophages).63-65 Conversely, stimulation of macrophages with Th2 cytokines, such as IL-4 or IL-13, immune complexes plus TLR ligands, IL-10, transforming growth factor-β, or glucocorticoids induces the generation of M2-type macrophages (also called alternatively activated macrophages).63-65 M1 macrophages produce high amounts of proinflammatory cytokines and NO by expressing inducible NO synthase and are important for eradicating bacterial, viral, and fungal infections.63-65 M2 macrophages are characterized by their high expression of markers of alternative activation, such as arginase-1, Chitinase 3-like 3 (also called YM-1), and found in inflammatory zone 1 (FIZZ1), and regulate responses to parasite infection, tissue remodeling, ...

Tumor-associated macrophages (TAMs) have an ambiguous and complex role in the carcinogenic process, since these cells can be polarized into different phenotypes (proinflammatory, antitumor cells or anti-inflammatory, protumor cells) by the tumor microenvironment. Given that the interactions between tumor cells and TAMs involve several players, a better understanding of the function and regulation of TAMs is crucial to interfere with their differentiation in attempts to skew TAM polarization into cells with a proinflammatory antitumor phenotype. In this study, we investigated the modulation of macrophage tumoricidal activities by the lectin jacalin. Jacalin bound to macrophage surface and induced the expression and/or release of mainly proinflammatory cytokines via NF-|i|κ|/i|B signaling, as well as increased iNOS mRNA expression, suggesting that the lectin polarizes macrophages toward the antitumor phenotype. Therefore, tumoricidal activities of jacalin-stimulated macrophages were evaluated. High

Tumor-associated macrophages (TAMs) are the multifarious group of cells that originate mainly from the peritumoral tissue or bone marrow and can be divided into two main types: M1 and M2. Among them are the infiltrating M1 tumor-associated macrophages present in the early stages of tumorigenesis, which can secrete proinflammatory cytokines and in turn inhibit tumor growth. On the contrary, M2 tumor-associated macrophages are predominant in the late stage of tumor formation. Type II cytokines, which are secreted by them, can promote anti-inflammatory reaction and thus promote tumor growth. However, it remains unclear when M1 tumor-associated macrophages are transformed to M2 tumor-associated macrophages, but tumor hypoxia is currently thought to be associated with such a shift. M2 tumor-associated macrophages secrete many proteases such as cathepsin, cytokines, and an epidermal growth factor. The presence of M2 TAMs make the tumor prone to growth and angiogenesis, which in turn damages other ...

Soluble products from antigen stimulated Trypanosoma cruzi-immune spleen cells enhanced the expression of Ia antigens on proteose-peptone-elicited mouse peritoneal macrophages (M phi). Acquisition of Ia paralleled M phi activation, previously shown to be mediated by this same source of lymphokine (LK). Expression of Ia and four other plasma membrane antigens was monitored by quantitative binding and radioautographic studies with 125I-monoclonal antibodies. Immune LK selectively enhanced expression of Ia and, to a lesser extent, H-2D relative to control LK from antigen-stimulated noninfected spleen. The levels of three other non-major histocompatibility complex (MHC) antigens, including the trypsin-resistant Fc receptor, were similar in cells exposed to both sources of LK. As little as 1% immune LK induced one-half maximal expression of Ia. Kinetic studies revealed that much of the Ia on freshly explanted peritoneal M phi was lost during the 1st d of culture. In the continued presence of immune ...

TY - JOUR. T1 - Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. AU - Ziegler, H. K.. AU - Unanue, E. R.. PY - 1982/1/1. Y1 - 1982/1/1. N2 - This paper describes the effects of two lysosomotropic compounds, ammonia and chloroquine, on the interaction of mononuclear phagocytes with immune T cells. The uptake and ingestion of Listeria monocytogenes by macrophages were not affected by the drugs; however, the macrophage catabolism of 125I-labeled Listeria was reduced in a dose-dependent way. The macrophage presentation of Listeria to T cells, an I-region-dependent phenomenon, was also inhibited. The degree of inhibition of catabolism paralleled that of antigen presentation. The inhibition of antigen presentation took place if the macrophages were treated before and during Listeria uptake; minimal inhibition took place if the macrophages were treated 30 min after Listeria ingestion, at which time a ...

The engulfing, bactericidal and degrading activities toSalmonella typhi, strain ty2-4446 and 0-901 and toSalmonella enteritidis of guinea pig macrophages obtained from peritoneal exudate, spleen and bone marrow that were cultivated for 2-7 days, were studied. The phagocytic activity was expressed as a total number of phagocytosed microbes and the number of viable bacteria, released from mechanically disrupted macrophages. The ratio of phagocytosed bacteria to the original number of bacteria that were introduced to macrophage cultures, were evaluated in per cents. No significant difference in phagocytic activity was found between macrophages submitted to thein vitro cultivation and macrophages freshly isolated from the organism. Profound variations in phagocytic activity of cells were found which were partially dependent on the dose of microbes employed for the infection of cultures. Furthermore, both the engulfing and bactericidal activity of peritoneal macrophages toSalmonella typhi were found to be

TY - JOUR. T1 - Biochemical and genetic characterization of the multidrug resistance phenotype in murine macrophage-like J774.2 cells. AU - Kirschner, Lawrence S.. AU - Greenberger, Lee M.. AU - Hsu, Stephen I Hong. AU - Yang, Chia-Ping H.. AU - Cohen, Dalia. AU - Piekarz, Richard L.. AU - Castillo, Gonzalo. AU - Han, Edward Kyu Ho. AU - Yu, Lijia. AU - Band Horwitz, Susan. PY - 1992/1/9. Y1 - 1992/1/9. N2 - The development of multidrug resistance (MDR) in malignant tumors is a major obstacle to the treatment of many cancers. MDR sublines have been derived from the J774.2 mouse macrophage-like cell line and utilized to characterize the phenotype at the biochemical and genetic level. Two isoforms of the drug resistance-associated P-glycoprotein are present and distinguishable both electrophoretically and pharmacologically. Genetic analysis has revealed the presence of a three-member gene family; expression of two of these genes, mdr1a and mdr1b, is associated with MDR whereas the expression of ...

Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from 18 patients with a variety of conditions. For each patient the percentages of AM showing the following properties were determined: (1) staining for the enzymes non-specific esterase (NSE) and acid phosphatase (ACP); (2) in vitro phagocytosis of Candida guillermondii; (3) expression of cell surface markers detected by two monoclonal antibodies (MoAb) (1B5 and DA2) and two anti-monocyte/macrophage MoAb (UCHMI and RFD2); and (4) simultaneous phagocytosis of C. guillermondii and staining with the MoAb. In all patients the majority of AM were found to be Ia positive (90 +/- 10%) ACP positive (100%) and NSE positive (97 +/- 4%). In contrast a smaller proportion were UCHM1 and RFD2 positive (77 +/- 11%, 68 +/- 12%) and less were phagocytic (37 +/- 17%). Whilst the total percentage of cells staining with the MoAb was unaltered by phagocytosis, the proportion of UCHM1 or RFD2 positive cells was significantly higher in the phagocytic

Immortalized Murine Macrophage Cell Line as a Model for Macrophage Polarization into Classically Activated M(IFNγ+LPS) or Alternatively Activated M(IL-4) Macrophages Abstract.

X X CHIA1, D NIKOLIC-PATERSON1,2, G TESCH1,2. 1Department of Nephrology, Monash Health, Clayton, Australia, 2Centre for Inflammatory Diseases, Monash University, Clayton, Australia. Aim: To investigate the role of spleen tyrosine kinase (SYK) in inflammatory cell signalling pathways in macrophages.. Background: SYK is expressed in B-lymphocytes and myeloid cells. Inhibition of SYK has been shown to prevent or reduce disease severity in animal models of inflammatory kidney disease, including LPS-induced acute kidney injury. This protection is associated with reduced expression of monocyte chemoattractant protein-1 (MCP-1), an important chemokine recruiting macrophages to sites of inflammation.. Methods: LPS stimulation assay was performed in cultured primary mouse bone marrow-derived macrophages (BMMac) and RAW264.7 murine macrophage cells. SYK inhibition was achieved using an SYK inhibitor (SYKi), GS-492429, and Sykf/f Csf1rCre mice with selective Syk gene knockout in myeloid cells. RNA ...

Mammalian macrophages can adopt polarization states that, depending on the exact stimuli present in their extracellular environment, can lead to very different functions. Although these different polarization states have been shown primarily for macrophages of humans and mice, it is likely that polarized macrophages with corresponding phenotypes exist across mammals. Evidence of functional conservation in macrophages from teleost fish suggests that the same, or at least comparable polarization states should also be present in teleosts. However, corresponding transcriptional profiles of marker genes have not been reported thus far. In this study we confirm that macrophages from common carp can polarize into M1- and M2 phenotypes with conserved functions and corresponding transcriptional profiles compared to mammalian macrophages. Carp M1 macrophages show increased production of nitric oxide and a transcriptional profile with increased pro-inflammatory cytokines and mediators, including il6, il12 and saa.

In this report, we show that blockade of CSF1/CSF1R signaling in pancreatic tumors depletes CD206Hi TAMs and reprograms remaining macrophages to support antitumor immunity. The blockade alone modestly enhances antitumor IFN responses, promotes CTL infiltration, and slows tumor progression. However, the therapeutic effect is limited by the induction of T-cell checkpoint molecules, including PDL1 on tumor cells and CTLA4 on T cells. Addition of the CSF1/CSF1R blockade markedly improved the efficacy of αPD1 and αCTLA4 checkpoint immunotherapy and led to the regression of even well-established PDAC tumors. These data suggest that CSF1/CSF1R signaling may be an effective therapeutic target to reprogram the immunosuppressive microenvironment of human PDAC tumors and enhance the efficacy of immunotherapy.. Recent data from several groups suggest that inhibition of CSF1R signaling alters the immunologic responses of tumor-infiltrating macrophages in several cancer types (10-12, 31-33). Mok and ...

The atherosclerotic plaque is characterised by the presence of macrophage foam cells that arise from dysfunctional cholesterol metabolism and trafficking. Cytokines are highly expressed within the plaque and play a critical function in initiating and augmenting the disease state. Previous studies have shown that the novel cytokine, interleukin-33 (IL-33), exerts anti-atherogenic actions in animal and in vitro models of the disease. The effect of IL-33 on pro-atherosclerotic markers was assessed in human THP-1 and murine RAW264.7 macrophages and primary human monocyte-derived macrophages (HMDMs) by real time-quantitative polymerase chain reaction (RT-qPCR). The studies then focused on characterising the signalling pathways involved in the regulation of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) expression by IL-33. The expression of key signalling components implicated in atherosclerosis were knocked down by RNA interference (RNAi). These experiments ...

The generation of T helper cells in vitro requires macrophages or macrophage-derived factors such as genetically related macrophage factor (GRF) or nonspecific macrophage factor (NMF). However, there is a basic difference of T helper cell induction when using particulate antigens. The present study demonstrates that this difference is based on the activation of two different T cell subsets. GRF activates short-lived T1 cells which amplify the induction of T2 cells, which are the helper cell precursors. Thus, the genetic restriction of T helper cell induction seen with soluble antigen or GRF lies on the level of macrophage or GRF interaction with T1 cells. NMF (or macrophages) and particulate antigens directly activate the helper cell precursor (T2) indicating no requirement for T1-T2 cooperation. The direct activation of the helper cell precursor with particulate antigens does not require histocompatible macrophages or NMF from histocompatible macrophages. The present results may explain some of the

Pharmacological interference with vacuolar-type H(+)-ATPase (V-ATPase), a proton-translocating enzyme involved in protein transport and pH regulation of cell organelles, is considered a potential strategy for cancer therapy. Macrophages are critically involved in tumor progression and may occur as pro-tumoral M2 phenotype, whereas classically-activated M1 can inhibit tumor development for example by releasing tumor-suppressing molecules, including tumor necrosis factor (TNF)alpha. Here, we show that targeting V-ATPase by selective inhibitors such as archazolid upregulates the expression and secretion of TNFalpha in lipopolysaccharide (LPS)- or LPS/interferon (INF)gamma-activated M1-like macrophages derived from human blood monocytes. In contrast, archazolid failed to elevate TNFalpha production from uncommitted (M0) or interleukin (IL)-4-treated M2-like macrophages. Secretion of other relevant cytokines (i.e., IL-1beta, IL-6, IL-10) or chemokines (i.e. IL-8 and monocyte chemotactic protein-1) ...

Tumour stromal macrophages differentiate to tumour-associated macrophages (TAMs) with characteristics of immunosuppressive M2-type macrophages, having a central role in promoting tumour vascularisation, cancer cell dissemination and in suppressing anti-cancer immune responses. Bisphosphonates (BPs) are a group of drugs commonly used as anti-resorptive agents. Further, nitrogen containing BPs like Zoledronate (ZOL), are known to cause unspecific inflammatory reactions hence the hypothesis that its use could modulate TAMs polarization toward a more inflammatory phenotype. We studied the in vitro polarization of J774 murine macrophages upon culture in 4T1 breast cancer cell-conditioned medium (4T1CM) and stimulation with LPS and free and liposome-encapsulated bisphosphonates. In this system, breast cancer soluble factors reduced the pro-inflammatory activation of macrophages but increased the secretion of matrix metalloproteinases (MMPs). In the presence of 4T1CM, a non-cytotoxic dose of liposome

View more ,The current RIKEN transcript set represents a significant proportion of the mouse transcriptome but transcripts expressed in the innate and acquired immune systems are poorly represented. In the present study we have assessed the complexity of the transcriptome expressed in mouse macrophages before and after treatment with lipopolysaccharide, a global regulator of macrophage gene expression, using existing RIKEN 19K arrays. By comparison to array profiles of other cells and tissues, we identify a large set of macrophage-enriched genes, many of which have obvious functions in endocytosis and phagocytosis. In addition, a significant number of LPS-inducible genes were identified. The data suggest that macrophages are a complex source of mRNA for transcriptome studies. To assess complexity and identify additional macrophage expressed genes, cDNA libraries were created from purified populations of macrophage and dendritic cells, a functionally related cell type. Sequence analysis revealed ...

The immediate tissue microenvironment of implanted biomedical devices and engineered tissues is highly influential on their long term fate and efficacy. The creation of a long-term anti-inflammatory microenvironment around implants and artificial tissues can facilitate their integration. Macrophages are highly plastic cells that define the tissue reactions on the implanted material. Local control of macrophage phenotype by long-term fixation of their healing activities and suppression of inflammatory reactions are required to improve implant acceptance. Herein, we describe the development of a cytokine cocktail (M2Ct) that induces stable M2-like macrophage phenotype with significantly decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine secretion profile. The positive effect of the M2Ct was shown in an in vitro wound healing model; where M2Ct facilitated wound closure by human fibroblasts in co-culture conditions. Using a model for induction of inflammation by LPS we have ...

Macrophages were first identified by Elie Metchnikoff more than a century ago as cells essential for host defense. Despite the fact that macrophages are one of the oldest immune cells known to man, this field is currently undergoing a thrilling revival as recent technological advances have revealed the fascinating diversity of macrophages and their essential functions in tissue homeostasis, wound healing, morphogenesis, cancer and metabolism. Importantly, it is now clear that macrophages in inflamed tissues comprise distinct subsets that differ in cellular origin and functional specialization.. This complexity has forced researchers to develop new tools to study the role of these intriguing cells in health and disease. Technological advances now permit the transcriptomic profiling and precise tissue localization of macrophages at the single-cell level, but these advances also bring puzzling questions regarding the inter- and intracellular networks that control macrophage function.. To help meet ...

In our bitransgenic mouse model, we demonstrate that hypoxia provokes an accumulation of alternatively activated alveolar macrophages that precedes the development of pulmonary hypertension and appears to play a critical role in the pathogenesis of disease. Overexpression of HO-1 induced a switch in macrophage polarity toward an anti-inflammatory phenotype, and this effect was associated with protection from HPH.. Hypoxia resulted in alveolar inflammation that consisted predominantly of macrophages. These findings correlate with the fact that macrophages tend to accumulate in poorly vascularized areas with low oxygen tension,29 and correlates with previous studies in HPH that highlighted the predominant role of the monocyte/macrophage lineage in modulating vascular remodeling.8 Additionally, we found that hypoxia in vivo and in vitro polarized the population of alveolar macrophages toward the M2 phenotype. Hypoxic microenvironment is also a hallmark feature of tumors, and similar to the hypoxic ...

Results Natural anti-oxLDL IgM monoclonal antibody 3A6 specifically inhibited the binding of CuoxLDL to naïve macrophages in vitro. 3A6 failed to inhibit the binding of CuoxLDL to LPS-activated macrophages and promoted the formation of CuoxLDL-mediated foam macrophages. Furthermore, 3A6 F (ab′)2 or pre-incubation with un-related IgM inhibited the binding of 3A6/CuoxLDL complex to LPS-activated macrophages, suggesting that the Fcα/μ receptor may be responsible for the binding of 3A6/CuoxLDL complex to LPS-activated macrophages. Indeed, LPS up-regulated the expression of Fcα/μ receptor in macrophages in a dose- and time-dependent manner, which was diminished by treatment with anti-TLR4 neutralising mAb. In addition, LPS induced the phosphorylation of p38MAPK and translocation of NF-kB p65, contributing to the up-regulated expression of Fcα/μ receptor in macrophages as treatment with specific inhibitor for p38MAPK (SB203580) or NF-kB (PDTC) attenuated the up-regulation of Fca/m receptor ...

The interactions established between macrophages and cancer cells are largely dependent on instructions from the tumour microenvironment. Macrophages may differentiate into populations with distinct inflammatory profiles, but knowledge on their role on cancer cell activities is still very scarce. In this work, we investigated the influence of pro-inflammatory (LPS-stimulated) and anti-inflammatory (IL-10-stimulated) macrophages on gastric and colorectal cancer cell invasion, motility/migration, angiogenesis and proteolysis, and the associated molecular mechanisms. Following exposure of gastric and colon cancer cell lines to LPS- and IL-10-stimulated human macrophages, either by indirect contact or conditioned media, we analyzed the effect of the different macrophage populations on cancer cell invasion, migration, motility and phosphorylation status of EGFR and several interacting partners. Cancer-cell induced angiogenesis upon the influence of conditioned media from both macrophage populations was

Peritoneal macrophages are 1 of the most studied macrophage populations in the physical body, yet the composition, developing mechanisms and origin ruling the maintenance of this compartment are debatable. Early research recommend that macrophages are component of a under the radar mononuclear phagocyte program, replenished by moving bloodstream monocytes1 constantly,2. Even more latest research propose that tissues macrophages derive from embryonic progenitors that seedling tissue during advancement3,4, and are taken care of autonomously from regular haematopoiesis by self-renewal and/or longevity5 eventually,6,7. Whether all macrophages are similarly able of self-renewal or if progenitor cells can be found within the inhabitants is certainly uncertain. Whereas growth within the alveolar macrophage area is certainly reported to occur stochastically6, clonal self-renewal among Langerhans cells suggests the presence of local progenitors8. However, the paradigm has now shifted once again, as a ...

M1 macrophages are more effective in the induction of the inflammatory response and clearance of Mycobacterium tuberculosis than M2 macrophages. Infected C57BL/6 mice generate a stronger cellular immune response compared with BALB/c mice. We hypothesized that infected C57BL/6 mice would exhibit a higher frequency and function of M1 macrophages than infected BALB/c mice. Our findings show a higher ratio of macrophages to M2 macrophages in the lungs of chronically infected C57BL/6 mice compared with BALB/c mice. However, there was no difference in the functional ability of M1 and M2 macrophages for the two strains in vitro. In vivo, a deleterious role for M2 macrophages was confirmed by M2 cell transfer, which rendered the infected C57BL/6, but not the BALB/c mice, more susceptible and resulted in mild lung inflammation compared with C57BL/6 mice that did not undergo cell transfer. M1 cell transfer induced a higher inflammatory response, although not protective, in infected BALB/c mice compared with their

Unkeless, J C., The presence of two fc receptors on mouse macrophages. Evidence from a variant cell line and differential trypsin sensitivity. (1977). Subject Strain Bibliography 1977. 2386 ...

Looking for online definition of macrophage/monocyte inhibitory factor in the Medical Dictionary? macrophage/monocyte inhibitory factor explanation free. What is macrophage/monocyte inhibitory factor? Meaning of macrophage/monocyte inhibitory factor medical term. What does macrophage/monocyte inhibitory factor mean?

The cellular mechanisms which account for the formation of osteoclasts and bone resorption associated with enlarging benign and malignant mesenchymal tumours of bone are uncertain. Osteoclasts are marrow-derived, multinucleated, bone-resorbing cells which express a macrophage phenotype. We have determined whether tumour-associated macrophages (TAMs) isolated from benign and malignant mesenchymal tumours are capable of differentiating into osteoclasts. Macrophages were cultured on both coverslips and dentine slices for up to 21 days with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) and human macrophage colony-stimulating factor (M-CSF) or, in the absence of UMR 106 cells, with M-CSF and RANK ligand. In all tumours, the formation of osteoclasts from CD14-positive macrophages was shown by the formation of tartrate-resistant-acid-phosphatase and vitronectin-receptor-positive multinucleated cells which were capable of carrying out lacunar resorption. These results

TY - JOUR. T1 - Increased muscle proteolysis after local trauma mainly reflects macrophage-associated lysosomal proteolysis. AU - Farges, M C AU - Balcerzak, Denis Pierre. AU - Fisher, B D AU - Attaix, D AU - Bechet, D AU - Ferrara, M AU - Baracos, V E PY - 2002/2. Y1 - 2002/2. N2 - Rat gastrocnemius showed increased protein degradation (+75-115%) at 48 h after traumatic injury. Injured muscle showed increased cathepsin B activity (+327%) and mRNA encoding cathepsin B (+670%), cathepsin L (+298%), cathepsin H (+159%), and cathepsin C (+268%). In in situ hybridization, cathepsin B mRNA localized to the mononuclear cell infiltrate in injured muscle, and only background levels of hybridization were observed either over muscle cells in injured tissue or in uninjured muscle. Immunogold/electron microscopy showed specific staining for cathepsin B only in lysosome-like structures in cells of the mononuclear cell infiltrate in injured muscle. Muscle cells were uniformly negative in the ...

TY - JOUR. T1 - Liver macrophage-associated inflammation correlates with SIV burden and is substantially reduced following cART. AU - Fisher, Bridget S.. AU - Green, Richard R.. AU - Brown, Rachel R.. AU - Wood, Matthew P.. AU - Hensley-McBain, Tiffany. AU - Fisher, Cole. AU - Chang, Jean. AU - Miller, Andrew D.. AU - Bosche, William J.. AU - Lifson, Jeffrey D.. AU - Mavigner, Maud. AU - Miller, Charlene J.. AU - Gale, Michael. AU - Silvestri, Guido. AU - Chahroudi, Ann. AU - Klatt, Nichole R.. AU - Sodora, Donald L.. N1 - Funding Information: This project was supported by funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health grant R21AI100782 (DLS) (https://www.niaid.nih.gov/) and funds from the National Institute of Dental and Craniofacial Research, National Institutes of Health grant R01DE023047 (DLS) (https://www.nidcr.nih.gov/). Research was also supported in part with Federal funds from the National Institute of Allergy and Infectious Diseases, ...

TY - JOUR. T1 - Expression of Gα(i2) mimics several aspects of LPS priming in a murine macrophage-like cell line. AU - Kugi, M.. AU - Kitamura, K.. AU - Cottam, G. L.. AU - Miller, R. T.. PY - 1995/1/1. Y1 - 1995/1/1. N2 - Priming of macrophages with low concentrations of lipopolysaccharide (LPS) enhances the ability of substances that act through heterotrimeric G proteins to stimulate immune cell functions. Although LPS-induced alterations in the expression and functions of G proteins of the α(i) family have been reported in hematopoietic cells, their effects on subsequent steps in LPS priming of macrophages have not been defined. To study the role of Gα(i2) in priming of macrophages by LPS, we expressed a mutant, activated form of α(i2) (α(i2Q2051)) in P388D1 cells, and compared its effects on PAF-dependent Ca signalling and arachidonic acid release to those in cells treated with LPS. In control P388D1 cells, treatment with LPS (100 ng/ml) for 1 hr increased the amount of α(i2) protein ...

Salmonella typhimurium invades host macrophages and can either induce a rapid cell death or establish an intracellular niche within the phagocytic vacuole. Rapid cell death requires the Salmonella pathogenicity island (SPI)1 and the host protein caspase-1, a member of the pro-apoptotic caspase family of proteases. Salmonella that do not cause this rapid cell death and instead reside in the phagocytic vacuole can trigger macrophage death at a later time point. We show here that the human pathogen Salmonella typhi also triggers both rapid, caspase-1-dependent and delayed cell death in human monocytes. The delayed cell death has previously been shown with S. typhimurium to be dependent on SPI2-encoded genes and ompR. Using caspase-1(-/-) bone marrow-derived macrophages and isogenic S. typhimurium mutant strains, we show that a large portion of the delayed, SPI2-dependent death is mediated by caspase-1. The two known substrates of activated caspase-1 are the pro-inflammatory cytokines ...

TY - JOUR. T1 - Differential mRNA expression of prostaglandin receptor subtypes in macrophage activation. AU - Hubbard, Neil. AU - Lee, S. H.. AU - Lim, D.. AU - Erickson, Kent L. PY - 2001. Y1 - 2001. N2 - Assessing the regulation of macrophage receptors for prostaglandin (PGE2) is essential to understanding the control which that potent lipid mediator has in modulating macrophage activities. The purpose of this study was to assess the differential mRNA expression of PGE2 receptor subtypes (EP) during macrophage exposure to activating and transducing agents. RAW 264.7 macrophages constitutively expressed mRNA for EP2, EP3 and EP4 receptor subtypes. Messenger RNA for EP4 was expressed at a much higher level when compared to EP2 in unstimulated macrophages as assessed by kinetic quantitative RT-PCR. When macrophages were stimulated with LPS, EP2 mRNA levels were 12-fold higher when compared to unstimulated macrophages, while EP4 mRNA remained unchanged. Conversely, mRNA levels of both EP2 and EP4 ...

TY - JOUR. T1 - HIV-1 inhibits phagocytosis and inflammatory cytokine responses of human monocyte-derived macrophages to P. falciparum infected erythrocytes. AU - Ludlow, Louise E. AU - Zhou, Jingling. AU - Tippett, Emma Dawn. AU - Cheng, Wan-Jung. AU - Hasang, Wina. AU - Rogerson, Stephen J. AU - Jaworowski, Anthony. PY - 2012. Y1 - 2012. N2 - HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1(Ba-L) infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0-28) versus (34 (27-108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352-3,387) versus 1,552 (889-6,331); pg/mL; p = 0.0078) and IL-1beta (16 (7-21) versus 33 (27-65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and ...

Compared to the classical phagocytotic M1 macrophages, the alternatively polarized macrophages, called M2 macrophages, function as modulators of cellular and humoral immunity and as mediators of tissue repair and remodeling. Transforming growth factor beta 1 (TGFβ1) is the most important growth factor enhancing tissue repair and fibrosis, and is believed to be produced and released by a subpopulation of M2 macrophages (M2c) in response to IL-10, in contrast to M2a macrophages which are primarily anti-inflammatory. Prior work has shown that macrophages are the only inflammatory cells that infiltrate into the closed nucleus pulposus, and the number of macrophages is positively correlated with the severity of intervertebral disc degeneration. Moreover, there is evidence to suggest that macrophages may either directly play a role in phagocytosis, or synergistically regulate lumbar disc metabolism through a neuro-immune mechanism. Likewise, macrophage dysfunction can cause the aggregation, ...

Cellular proliferation and macrophage influx precede interstitial fibrosis in cyclosporine nephrotoxicity is an eagle-i resource of type Journal article at eagle-i Network Shared Resource Repository.

TY - JOUR. T1 - Elevated A20 contributes to age-dependent macrophage dysfunction in the lungs. AU - Hinojosa, Cecilia A.. AU - Akula Suresh Babu, Ramya. AU - Rahman, Md M.. AU - Fernandes, Gabriel. AU - Boyd, Angela R.. AU - Orihuela, Carlos J.. N1 - Funding Information: We thank David E. Harrison and Kevin Flurkey at The Jackson Laboratory for their gift of aged mice. Financial support for CJO came from the Morrison Trust , The Glenn Foundation , and NIH AG033274 . Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 2014/6. Y1 - 2014/6. N2 - Advanced age is associated with chronic low-grade inflammation (i.e. inflamm-aging) and poor macrophage function that includes a weak pro-inflammatory cytokine response to bacteria and diminished phagocytosis (i.e. age-dependent macrophage dysfunction [ADMD]). One reason for this is that ADMD is associated with poor NFκB and MAPK activation following Toll-like receptor stimulation. Herein, we tested the hypothesis that inflamm-aging induces ...

ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. Therefore, signaling pathways that alter ER stressinduced apoptosis may affect advanced atherosclerosis. Here we placed Apoe/ mice deficient in macrophage p38α MAPK on a Western diet and found that they had a marked increase in macrophage apoptosis and plaque necrosis. The macrophage p38αdeficient lesions also exhibited a significant reduction in collagen content and a marked thinning of the fibrous cap, which suggests that plaque progression was advanced in these mice. Consistent with our in vivo data, we found that ER stressinduced apoptosis in cultured primary mouse macrophages was markedly accelerated under conditions of p38 inhibition. Pharmacological inhibition or genetic ablation of p38 suppressed activation of Akt in cultured macrophages and in atherosclerotic lesions. In addition, inhibition of Akt enhanced ER stressinduced macrophage ...

Tumor necrosis factor (TNF) alpha has been shown to be a major therapeutic target in rheumatoid arthritis with the success of anti-TNFalpha antibody clinical trials. Although signaling pathways leading to TNFalpha expression have been studied in some detail, there is evidence for considerable differences between individual cell types. This prompted us to investigate the intracellular signaling pathways that result in increased TNFalpha synthesis from macrophages in the diseased synovial joint tissue. Using an adenoviral system in vitro we report the successful delivery of genes to more than 95% of normal human macrophages. This permitted us to show, by using adenoviral transfer of IkappaB alpha, the natural inhibitor of NF-kappaB, that induction of TNFalpha in normal human macrophages by lipopolysaccharide, but not by some other stimuli, was inhibited by 80%. Furthermore the spontaneous production of TNFalpha from human rheumatoid joint cell cultures was inhibited by 75%, indicating that the NF-kappaB

Upregulation of macrophage plasma membrane and nuclear phospholipase D activity on ligation of the alpha2-macroglobulin signaling receptor: involvement of heterotrimeric and monomeric G proteins.

The results of this study show that changes in numbers of synovial sublining macrophages correlate with clinical improvement independently of the therapeutic strategy. Furthermore, this study demonstrates that the change in the numbers of sublining macrophages may be used to explain clinical outcome. Of importance, the data indicate that the change in the number of sublining macrophages could be used as a sensitive biomarker to predict possible efficacy of a new antirheumatic treatment.. Previous work suggested an association between the number of synovial macrophages and joint destruction in RA.14 Moreover, analysis of the synovial cell infiltrate demonstrated a positive correlation between scores for local disease activity and the number of macrophages as well as expression of macrophage derived cytokines (tumour necrosis factor α (TNFα) and interleukin (IL) 6) in rheumatoid ST, suggesting that macrophage numbers are associated with clinical signs of inflammation.2 In keeping with this ...

In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell-mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. We show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an ...

Mechanical stress has been recognized as a key inducer of bone regeneration in bone damage, which is experimentally mimicked by distraction osteogenesis (DO), a bone-regenerative process induced by post-osteotomy distraction of the surrounding vascularized bone segments, and realized by new bone formation within the distraction gap. The mechanisms that underlie the DO-induced bone regeneration remain poorly understood and a role of macrophages in the process has been inadequately studied. Here, in a mouse model of DO, we showed significant increase in macrophages in the regeneration area. Moreover, in a loss-of-function approach by depleting inflammatory macrophages, the bone regeneration was compromised by assessment of histology and molecular biology. Thus, our study demonstrates the necessary participation of inflammatory macrophages in the process of DO-induced bone regeneration, and suggests that targeting inflammatory macrophages may help to improve clinical bone repair.

Introduction: Macrophages comprise an essential component of the mammary microenvironment necessary for normal gland development. However, there is no viable in vivo model to study their role in normal human breast function. We hypothesized that adding primary human macrophages to the murine mammary gland would enhance and provide a novel approach to examine immune-stromal cell interactions during the humanization process. Methods: Primary human macrophages, in the presence or absence of ectopic estrogen stimulation, were used to humanize mouse mammary glands.

In both cells and animals, cannibalism can transfer harmful substances from the consumed to the consumer. Macrophages are immune cells that consume their own dead via a process called cannibalistic efferocytosis. Macrophages that contain harmful substances are found at sites of chronic inflammation, yet the role of cannibalism in this context remains unexplored. Here we take mathematical and experimental approaches to study the relationship between cannibalistic efferocytosis and substance accumulation in macrophages. Through mathematical modelling, we deduce that substances which transfer between individuals through cannibalism will concentrate inside the population via a coalescence process. This prediction was confirmed for macrophage populations inside a closed system. We used image analysis of whole slide photomicrographs to measure both latex microbead and neutral lipid accumulation inside murine bone marrow-derived macrophages (104-[Formula: see text]) following their stimulation into an

The present study affirms our hypothesis that the Notch pathway plays an important role in macrophages, a key cell type in inflammation and atherosclerosis. Evidence that supports this idea includes the expression of multiple Notch receptors and ligands in human macrophages; markedly increased Dll4 expression in human macrophages stimulated with LPS, mmLDL, or IL-1β, an event that likely involves TLR4 and NF-κB; the ability of Dll4 to bind to macrophages and trigger Notch signaling; the induction of the MAPK, Akt, and NF-κB pathways in macrophages stimulated with Dll4; the Dll4-induced transcription of iNOS, PTX3, Id1, and Dll4 itself; and the presence of Notch pathway components, such as Dll4 and Notch3, in human atherosclerotic plaques rich in macrophages.. Dll4 expression induced in human primary macrophages by proinflammatory stimuli (LPS, IL-1β, and mmLDL) (Figures 2 through 4⇑⇑) and the detection of immunoreactive Dll4 in human atherosclerotic plaques (Figure 8) indicate possible ...

BioAssay record AID 309254 submitted by ChEMBL: Reduction of Mycobacterium tuberculosis H37Rv growth in mouse peritoneal macrophage monolayers after 7 days.

Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to a variety of stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate (or polarize) macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate

Stewart, J; Glass, E J.; and Weir, D M., Macrophage binding of staphylococcus albus is blocked by anti i-region alloantibody. (1982). Subject Strain Bibliography 1982. 4410 ...

TY - JOUR. T1 - Niacin modulates macrophage polarization in Parkinsons disease. AU - Wakade, Chandramohan G.. AU - Giri, Banabihari. AU - Malik, Aneeq. AU - Khodadadi, Hesam. AU - Morgan, John Christopher. AU - Chong, Kwong Yew Raymond. AU - Baban, Babak. PY - 2018/7/15. Y1 - 2018/7/15. N2 - Neuroinflammation remains a central piece in Parkinsons disease (PD) pathophysiology. However, mechanisms by which PD links to the neuroinflammation remain elusive. Here, for the first time, we report that lower dose of niacin in PD patients may affect macrophage polarization from M1 (pro-inflammatory) to M2 (counter-inflammatory) profile through the niacin receptor GPR109A. Skew in the peripheral macrophages were accompanied by improved quality of life assessments in patients. Low dose niacin supplementation may be beneficial in PD, boosting anti-inflammatory processes and suppressing inflammation. Varied niacin dosages for longer durations may further reveal the potential role of anti-inflammatory ...

Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or produce proinflammatory cytokines. In vitro studies suggest this unique, functional phenotype is a result of the exposure of newly recruited blood monocytes to intestinal stromal products. However, in AIDS-related CMV colitis, mucosal macrophages express HIV-1 and proinflammatory cytokines. Therefore, we investigated the mechanism by which CMV confers permissiveness to HIV-1 and cytokine production on intestinal macrophages. We show that intestinal stroma-conditioned media (S-CM) down-regulated monocyte-derived macrophage infection by HIV-1 (pseudotyped with YU2 envelope or vesicular stomatitis virus glycoprotein) and production of TNF-α, but preinfection of the cells with CMV reversed this down-regulation, enhancing HIV-1 infection, p24 production, and TNF-α release. The ability of CMV to reverse S-CM down-regulation of macrophage HIV-1 infection was blocked by anti-TNF-α antibodies and ...

Inflammation plays a prominent role in atherosclerosis development and associated cardiovascular disease. Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development and clinical outcome. They are one of the most plastic cells of the hematopoietic system. In response to micro-environmental stimuli they adopt different polarization states driving their functional repertoire in tissue homeostasis, host defense and pathology. Whilst several efforts have been made to classify macrophages, the binary M1/M2 classification remains the most used and offers a useful reductionist framework to study and describe their function.. We described the association of macrophage subsets with specific regions in human atherosclerotic plaques. Inflammatory M1 macrophages associated with plaque rupture prone shoulder regions, while M2 macrophages dominated in the adventitia. A main focus of our research interest is on the targeting of macrophage ...

Interferon gamma (IFN-γ) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-γ induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-γ on macrophage activation. IFN-γ reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT+LIF cells) and BeWo cells (BW/ST+LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-γ. vCT+LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST+LIF cells

TY - JOUR. T1 - Regulation of mannose receptor synthesis and turnover in mouse J774 macrophages. AU - Fiani, Maria L.. AU - Beitz, Jill. AU - Turvy, Diane. AU - Blum, Janice S.. AU - Stahl, Philip D.. PY - 1998/7. Y1 - 1998/7. N2 - The mannose receptor, present on the plasma membrane of macrophages, promotes the internalization of glycoproteins and glycoconjugates via both endocytic and phagocytic pathways. The expression of this receptor is tightly modulated during monocyte/MΦ differentiation and cellular activation. We isolated clonal populations from murine J774 macrophage tumor cells, which differ in their surface expression of functional mannose receptors. To examine the potential mechanisms regulating receptor function in these cell lines, the interaction of receptor with ligand as well as receptor synthesis and degradation was analyzed. J774 clones with both high and low levels of mannose receptor activity were found to synthesize significant amounts of receptor protein, suggesting that ...

Purpose: The mechanism by which alveolar macrophages increase in patients with chronic obstructive pulmonary disease (COPD) is still unknown. CD163, CD204 and CD206 are known to be markers of M2 macrophages, which are a specific macrophage phenotype. We investigated the expression of CD163, CD204 and CD206 on alveolar macrophages in COPD patients.. Methods: Immunohistochemical techniques were used to examine CD163, CD204 and CD206 expression on alveolar macrophages in the lungs of COPD patients, smokers and non-smokers.. Results: The numbers of alveolar macrophages in COPD patients were significantly greater in smoked and non-smokers. The numbers and percentages of CD163+, CD204+ or CD206+ alveolar macrophages in patients with COPD at GOLD stages III and IV were significantly higher than in those at GOLD stages I and II, and those in smokers and non-smokers.. Conclusion: Overproduction of CD163, CD204 and CD206 on alveolar macrophages in the lungs may be involved in the pathogenesis of COPD. ...

Cigarette smoke (CS) is considered to be a major possible risk factor for pulmonary and intestinal inflammation. CS causes macrophages recruitment into the mucosa of both organs, and these cells promote inflammatory response by inducing uncontrolled secretion of inflammatory mediators, including cytokines, chemokine, and MMPs. In this study, we investigated whether macrophage depletion modulates the cigarette smoke (CS)-induced inflammatory response in both the lung and bowel. The mice were exposed to CS for 30 min, after which they were rested in a fresh air environment for 30 min. The total duration of exposure to CS was 2h per day for 4 weeks. Macrophage depletion state was made by injection of clodronate containing liposome. Individual body weights were measured twice a week, and the mice were sacrificed on day 28. Hematoxylin and eosin (H&E) staining was performed in the lung and colon tissue to determine histological changes. Inflammatory mediators synthesis was analyzed using ELISA and western

Keratinocytes and neurons cells are the main target for Herpes Simplex Virus Type 1 (HSV-1) invasion. Moreover, keratinocytes are the most abundant cell types in the epidermis layer in the skin. Therefore, they are the first cells to encounter HSV-1 in the primary infection. Next, the virus reaches the nerve endings and is transferred to neuronal cells as a result from the primary infection. In between these two events, innate immune cells including monocytes and macrophages response is activated and recruited to the infection site. In this study, keratinocytes (PAM-212) and murine macrophage (RAW 264.7) cell lines were utilized to investigate the response of macrophages (RAW 264.7 ) and keratinocytes (PAM-212) to HSV-1 infection and propagation in vitro. In this study, initially keratinocytes (PAM-212) and macrophages (RAW 264.7) and were studied either infected or uninfected with HSV-1 at MOI 0.1 in a monolayer model. Cell lines were co-cultured at ratio 1:5 (macrophages : keratinocytes) respectively

Alveolar tissue macrophage phagocytosis of E. coli, scanning electron micrograph (SEM). Note the macrophage has short filopodia that extend from the cell and aid in finding bacteria for phagocytosis. A tissue macrophage is a large, mature phagocyte that can ingest and destroy invading microbes, foreign particles, cancerous or diseased cells and cellular debris. Alveolar (lung pleural cavity) macrophages are part of the reticuloendothelial system. Magnification: x800 when shortest axis printed at 25 millimetres. - Stock Image C036/9773

Phagocytic cells are a critical line of defense against infection. The ability of a pathogen to survive and even replicate within phagocytic cells is a potent method of evading the defense mechanisms of the host. A number of pathogens survive within macrophages after phagocytosis and this contributes to their virulence. Salmonella is one of these pathogens. Here we report that 6-14 hr after Salmonella enters the macrophage and replicates, it resides in large vacuoles and causes the destruction of these cells. Furthermore, we identified four independently isolated MudJ-lacZ insertion mutants that no longer cause the formation of these vacuoles or kill the macrophages. All four insertions were located in the ompR/envZ regulon. These findings suggest that killing and escape from macrophages may be as important steps in Salmonella pathogenesis as are survival and replication in these host cells.. ...

The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters. Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test. The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In

TY - JOUR. T1 - Human lung macrophages enhance and inhibit lymphocyte proliferation. AU - Liu, M. C.. AU - Proud, D.. AU - Schleimer, R. P.. AU - Plaut, M.. PY - 1984/1/1. Y1 - 1984/1/1. N2 - To evaluate the effector functions of human lung macrophages, cell preparations containing 70 to 95% macrophages were obtained from surgically resected lungs of cancer patients and were co-cultured with allogeneic or autologous peripheral blood mononuclear cells (PBMC) and Con A. In contrast to previous reports of either marked stimulatory or inhibitory effects of human lung macrophages on lymphocyte function, the present results demonstrate that the proliferative response was a complex function of both the numbers of PBMC and macrophages. In the presence of low numbers of PBMC, small numbers of macrophages enhanced proliferation, whereas larger numbers inhibited proliferation; in the presence of larger numbers of PBMC, macrophages only inhibited. Inhibition was not mediated by cyclo-oxygenase products of ...

This is the first study to demonstrate distinct correlation of alveolar macrophage dysfunction with clinical predilection towards COPD exacerbations. Furthermore, this association occurred in response to NTHI, M catarrhalis, and S pneumoniae, the three most common respiratory pathogens in COPD.19 An evoked alveolar macrophage inflammatory response is critical for innate immune-mediated bacterial clearance. Occurrence of bacterial exacerbations is primarily driven by acquisition of new bacterial pathogens in the lower respiratory tract.2 Increased lower airway inflammation has been linked to increased respiratory symptoms in COPD leading to clinical exacerbations.20 With the introduction of new strains of respiratory pathogens and impaired macrophage clearance, bacteria persist. Failure to clear respiratory bacteria may promote exacerbations and require adaptive immune mechanisms for pathogen clearance.. We previously discovered that alveolar macrophages of adults with COPD had impaired ...

About 6 million Americans suffer from heart failure and 70% of heart failure cases are caused by myocardial infarction (MI). Following myocardial infarction, increased cytokines induce two major types of macrophages: classically activated macrophages which contribute to extracellular matrix destruction and alternatively activated macrophages which contribute to extracellular matrix construction. Though experimental results have shown the transitions between these two types of macrophages, little is known about the dynamic progression of macrophages activation. Therefore, the objective of this study is to analyze macrophage activation patterns post-MI. We have collected experimental data from adult C57 mice and built a framework to represent the regulatory relationships among cytokines and macrophages. A set of differential equations were established to characterize the regulatory relationships for macrophage activation in the left ventricle post-MI based on the physical chemistry laws. We further

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers in the human population. HCC is an inflammation-associated cancer caused by different etiological factors. The chronic inflammation leads to continuous cycles of hepatocytes destructive-regenerative process and contributes to HCC initiation and progression. Macrophages play a crucial role in chronic liver inflammation. The tumor microenvironment plays a key role in the progression of HCC. Tumor-associated macrophages are a well-known component of the tumor microenvironment and abundantly infiltrate HCC microenvironment. The roles of macrophages in the development and progression of HCC have been recognized. The deep understanding of macrophages in HCC will be critical for developing effective HCC therapy. Targeting of macrophages might provide novel therapeutic approaches for HCC patients and is an emerging field of interest. This review summarizes the knowledge on the contribution of macrophages in the development and

TY - JOUR. T1 - Recruitment of exogenous macrophages into metastases at different stages of tumor growth. AU - Bugelski, Peter J.. AU - Kirsh, Richard. AU - Buscarino, Charles. AU - Corwin, Steven P.. AU - Poste, George. PY - 1987/4/1. Y1 - 1987/4/1. N2 - The endogenous tumor-associated macrophage content and recruitment of labeled peritoneal exudate cells into experimental murine B16 melanoma metastases has been examined at different stages in the progressive growth of metastatic lesions. The recruitment of thioglycollate-elicited peritoneal exudate cells and peritoneal exudate cells activated in vitro with muramyl dipeptide was studied. Tumor-associated macrophages and labeled peritoneal exudate cells were identified in paraffin sections by specific histochemical staining and their density in individual metastases measured morphometrically. The density of tumor-associated macrophages and exogenously recruited peritoneal exudate cells was high in very small lesions but decreased rapidly as a ...