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 ...
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 ...
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 ...
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 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) 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 ...
Obesity is associated with low-grade chronic inflammation without bacterial or viral infection, but the triggers and molecular mechanisms that lead to obesity-associated metabolic inflammation remain to be further explored. Although recent studies demonstrated palmitate triggered thioglycollate-elicited macrophage death under the stimulation of Gram-negative bacteria-derived LPS (39, 40), it did not explain the sterile inflammation associated with obesity, and it also raised concerns regarding physiology and activated status of these thioglycollate-activated macrophages (41). In this article, we report that when various dietary FAs were uptaken by stable macrophage cell lines or primary BMMs, only sFAs (e.g., PA, SA) were metabolized to produce Cers to induce macrophage cell death. Most importantly, we identified A-FABP as a new molecular sensor in mediating excess sFA-induced Cer production and in promoting macrophage cell death, thus contributing to the sterile chronic inflammation in ...
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.
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) ...
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
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 ...
Using a mouse model of spinal injury, Michal Schwartz and colleagues tested the effect of macrophages on the recovery process and demonstrate an important anti-inflammatory role for a subset of infiltrating monocyte-derived macrophages that is dependent upon their expression of interleukin 10.
Polarization has been a useful concept for describing activated macrophage phenotypes and gene expression profiles. However, macrophage activation status within tumors and other settings are often inferred based on only a few markers. Complicating matters for relevance to human biology, many macrophage activation markers have been best characterized in mice and sometimes are not similarly regulated in human macrophages. To identify novel markers of activated human macrophages, gene expression profiles for human macrophages of a single donor subjected to 33 distinct activating conditions were obtained and a set of putative activation markers were subsequently evaluated in macrophages from multiple donors using integrated fluidic circuit (IFC)-based RT-PCR. Using unsupervised hierarchical clustering of the microarray screen, highly altered transcripts (>4-fold change in expression) sorted the macrophage transcription profiles into two major and 13 minor clusters. Among the 1874 highly altered transcripts,
Glass, C.K. (2001) Potential roles of the peroxisome proliferator-activated receptorγ in macrophage biology and atherosclerosis. Journal of Endo-crinology, 169, 461-464. doi10.1677/joe.0.1690461
Asthma is characterized by more IRF5+ M1 and CD206+ M2 macrophages and less IL10+ M2-like macrophages around airways compared to healthy airways. Draijer C, Boorsma CE, Robbe P, Timens W, Hylkema MN, Ten Hacken NH, van den Berge M, Postma DS, Melgert BN.
Macrophages in the gastrointestinal mucosa represent the largest pool of tissue macrophages in the body. In order to maintain mucosal homeostasis, resident intestinal macrophages uniquely do not express the lipopolysaccharide (LPS) co-receptor CD14 or the IgA (CD89) and IgG (CD16, 32, and 64) receptors, yet prominently display Toll-like receptors (TLRs) 3-9. Remarkably, intestinal macrophages also do not produce proinflammatory cytokines in response to TLR ligands, likely because of extracellular matrix (stromal) transforming growth factor-β (TGF-β) dysregulation of nuclear factor (NF)-κB signal proteins and, via Smad signaling, expression of IBα, thereby inhibiting NF-κB-mediated activities. Thus, in noninflamed mucosa, resident macrophages are inflammation anergic but retain avid scavenger and host defense function, an ideal profile for macrophages in close proximity to gut microbiota. In the event of impaired epithelial integrity during intestinal infection or inflammation, however, ...
Macrophages are remarkably plastic cells which in order to adapt to different tissue microenvironments can assume a range of different phenotypes. Accordingly, macrophages can exhibit either pro- or anti-inflammatory phenotypes and are routinely classified into M1 (classically activated) phenotype and M2 (alternatively activated) phenotype.[4] According to this classification, macrophages acquire M1 phenotype following in vitro stimulation with interferon gamma (IFN-γ) alone or in combination with TLR ligands (e.g. lipopolysaccharide (LPS)) whereas macrophages acquire M2 phenotype after in vitro exposure to IL-4 and IL-13. M1 macrophages secrete high levels of proinflammatory cytokines (e.g. tumor necrosis factor (TNF-α), IL-6, IL-1β) and generate reactive oxygen and nitrogen species such as nitric oxide via activation of inducible nitric oxide synthase (iNOS). Conversely, M2 macrophages activate arginase 1 (Arg1) that blocks iNOS activity and therefore inhibits nitric oxide production. They ...
The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus muscle after 10 days of hindlimb suspension and 2, 4, and 7 days after the resumption of weight bearing. Necrosis was identified using histological features, such as muscle fiber infiltration, and regeneration was identified using immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show that necrotic fibers in 2-day reloaded soleus muscle were invaded by ED1+ and Ia+ macrophages. The number of invaded fibers in muscles reloaded for 2 days increased to 2.8/mm2 compared with 0.2/mm2 in age-matched normal muscle but returned to control values by the 4th day of resumed weight bearing. In the interstitial spaces of 2-day recovery muscle, ED1+ and Ia+ macrophages numbered 369 and 332/mm2, respectively, compared with 12 and 72/mm2, respectively, in control soleus. After 7 days of reloading, the number of ED1+ cells
Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are significant components of the microenvironment of solid tumors in the majority of cancers. TAMs sequentially develop from monocytes into functional macrophages. In each differentiation stage, TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment (e.g., expression of immune checkpoint molecules, production of Treg-related chemokines and cytokines, production of arginase I). Although the main population of TAMs is immunosuppressive M2 macrophages, TAMs can be modulated into M1-type macrophages in each differential stage, leading to the suppression of tumor growth. Because the administration of certain drugs or stromal factors can stimulate TAMs to produce specific chemokines, leading to the recruitment of various tumor-infiltrating lymphocytes, TAMs can serve as targets for cancer immunotherapy. In this review, we discuss the differentiation, activation, and immunosuppressive function of TAMs, as well
TY - JOUR. T1 - Interleukin-4 regulates macrophage interleukin-12 protein synthesis through a c-fos mediated mechanism. AU - Roy, Sabita. AU - Charboneau, Richard. AU - Melnyk, Dean. AU - Barke, Roderick A.. PY - 2000/1/1. Y1 - 2000/1/1. N2 - Background. Interleukin-4 (IL-4) treatment after lipopolysaccharide (LPS) induction inhibits macrophage (Mφ) IL-12 synthesis; however, IL-4 pretreatment (PreTx) primes the Mφ for increased LPS-induced IL-12 production. In this study we study the role of c-fos in the IL-4 priming of Mφ IL-12 synthesis. Methods. With a murine in vitro peritoneal Mφ model, we studied the effect of either c-fos deficiency (wild type, WT; homozygous c-fos knockout, Homo KO) or c-fos overexpression to study the role of c-fos in IL-4 priming of LPS-induced Mφ IL-12 synthesis. Results. (1) We first show that IL-4 PreTx results in a 72% decrease in Mφ c-fos mRNA compared with vehicle PreTx. (2) With respect to IL-12 p70 protein, IL-4 PreTx in the WT group increased LPS-induced ...
Cell Culture. The murine macrophage cell line J774A.1 was grown in RPMI 1640 medium (Invitrogen, Carlsbad, CA) supplemented with 100 U/ml penicillin, 100 μg/ml streptomycin, 50 μg/ml gentamicin, 20 U/ml polymyxin B, and 10% fetal bovine serum. Alternatively, peritoneal macrophages were isolated 5 days after injection of 2 ml of Brewers thioglycolate medium (Sigma-Aldrich, St. Louis, MO) into the peritoneal cavity of C56BL/6 mice as reported previously (McCarron et al., 1984). Primary macrophages were added to culture flasks and allowed to adhere for 2 h at 37°C. Nonadherent cells were removed by three washes of warm medium. Adherent cells were ,99% macrophages as assessed by immunocytochemical detection of the macrophage marker F4/80 (anti-F4/80, clone Cl:A3-1; Serotec, Oxford, UK). Smooth muscle cells were isolated from mouse or rabbit aorta by collagenase type 2 (Worthington, Lakewood, NJ) and elastase (Sigma-Aldrich) digestion (60-90 min at 37°C) at 300 and 5 U/ml final concentration, ...
How fish farming might spawn disease, brain pacemakers might reduce dementia and macrophages might help the heart keep the beat.
Diabetic cardiomyopathy (DCM) is a common complication of diabetes and is characterized by chronic myocardial inflammation. Mesenchymal stem cell (MSC) infusions have recently been suggested to alleviate myocardial injury and ameliorate cardiac function. However, few studies have focused on the effects of MSCs in DCM. Therefore, we explored the effects of MSC-regulated macrophage polarization on myocardial repair in DCM. A DCM rat model was induced by a high-fat diet and streptozotocin (STZ) administration and infused 4 times with MSCs. Rat blood and heart tissue were analyzed for blood glucose levels, lipid levels, echocardiography, histopathology, macrophage phenotype ratios and inflammatory cytokines, respectively. We mimicked chronic inflammation in vitro by inducing peritoneal macrophages with high glucose and LPS, then cocultured these macrophages with MSCs to explore the specific mechanism of MSCs on macrophage polarization. DCM rats exhibited abnormal blood glucose levels and lipid metabolism,
The regulation of macrophage activator protein-1 (AP-1) gene expression by LPS and cytokines is of potentially crucial importance in the pathogenesis of several diseases. The action of LPS and four cytokines on AP-1 gene expression in the murine macrophage J774.2 cell line was, therefore, studied. Exposure of the cells to IL-6 produced no changes in the mRNA levels of all AP-1 members studied. In contrast, the expression of JunB, c-jun and c-fos, but not JunD, was increased by LPS, TNF-α, IFN-γ and IL-1, albeit with different kinetics and magnitude of induction. Electrophoretic mobility shift assays showed a close correlation between the expression of the AP-1 genes and the functional AP-1 DNA binding activity and, additionally, demonstrated the participation of heterodimeric interactions between the different members. These studies provide insights into the potential mechanisms that may be involved in the mediator-specific modulation of AP-1 regulated macrophage gene expression.. ...
Epigenetic control of macrophage differentiation is tissue-specific. Relative to dendritic cells, tissue macrophages poorly present antigens to other immune cells and fail to migrate to regional lymph nodes (22). Transcriptomic profiling of four tissue-resident macrophage populations by the ImmGen consortium revealed that macrophages from different tissues - brain microglia, splenic red pulp macrophages, large peritoneal macrophages, and Kupffer cells in the liver - had more differences in their transcriptional program than similarities (23). In contrast, dendritic cells recovered from a variety of tissues had more similar transcriptomes. These findings suggested that tissue-resident macrophages were uniquely defined by factors originating from their microenvironment. In seminal studies, two groups of investigators used transcriptional and epigenomic profiling of tissue-resident macrophage populations to provide insights into the molecular events that allow monocytes to differentiate along ...
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects alveolar macrophages following aerosol transmission. Lung macrophages provide a critical intracellular niche that is required for Mtb to establish infection in the human host. This parasitic relationship is made possible by the capacity of Mtb to block phagosome maturation following entry into the host macrophage, creating an environment that supports bacillary replication. Apoptosis is increasingly understood to play a role in host defense against intracellular pathogens including viruses, fungi, protozoa and bacteria. In the last 15 years an understanding of the role that macrophage apoptosis plays in TB has begun to emerge. Here we review the history and current state of the art of this topic and we offer a model of the macrophage-pathogen interaction that takes into the account the complexities of programmed cell death and the relationship between various death signaling pathways and host defense in TB.
Macrophage-enriched peritoneal exudate cells from mice infected with Mycobacterium bovis BCG, macrophage-like tumor cells (PU 5-1.8), and peritoneal macrophages propagated in vitro with macrophage growth factor released tumoricidal activity into the culture medium within 2 to 3 h after stimulation with nanogram quantities of bacterial lipopolysaccharide. The cytotoxic activities from each of the macrophage culture supernatants eluted from diethylaminoethyl-Sephacel columns at a sodium chloride concentration of 200 mM exhibited a molecular weight of 50,000 to 60,000 as estimated by gel filtration, were stable at 56 degrees C for 30 min, and were active at a pH range of 6 to 10. A rabbit antiserum directed against serum-derived cytotoxic activity (tumor-necrotizing factor) from BCG-infected and lipopolysaccharide-challenged mice inhibited all of the cytotoxic activities generated in vitro. This suggests that the macrophage-derived cytotoxins are identical with serum-derived cytotoxic factor, which ...
TY - JOUR. T1 - Distinct localization of GLUT-1, -3, and -5 in human monocyte-derived macrophages. T2 - Effects of cell activation. AU - Malide, Daniela. AU - Davies-Hill, Theresa M.. AU - Levine, Mark. AU - Simpson, Ian. PY - 1998/3/1. Y1 - 1998/3/1. N2 - We determined subcellular localization of GLUT-1, GLUT-3, and GLUT-5 as human monocytes differentiate into macrophages in culture, and effects of the activating agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA). Western blot analysis demonstrated progressively increased GLUT-1, rapidly decreased GLUT-3, and a delayed increase of GLUT-5 expression during differentiation. Confocal microscopy revealed that each isoform displayed a unique subcellular distribution and cell-activation response. GLUT-1 was localized primarily to the cell surface but was also detected in the perinuclear region in a pattern characteristic of recycling endosomes. GLUT-3 exhibited predominantly a distinct vesicle-like staining but ...
Figure 6. Accumulation of activated macrophages in tumors following PD-L1 antibody treatment and inhibited tumor growth in Rag−/− mice treated with PD-L1 antibody. B16 melanoma cells were injected into C57Bl/6 mice and the mice were treated with PBS, irrelevant isotype, or PD-L1 antibody. Tumor, spleen, and lymph node tissue was harvested for flow-cytometric analysis of macrophage populations (A) and percentages of tumor macrophages and T cells are shown in B. We also measured surface expression of tumor macrophage MHC II (C) by flow cytometry, and tumor tissues were stained for F4-80 (green) and MHC II (red) expression before counterstaining with DAPI (blue) for imaging at 10× magnification (D). Statistical comparison of cell numbers and expression of surface markers were conducted by two-way ANOVA using Prism7 software. These data are representative of two repeated experiments with four mice in each group. Next, PyMT breast carcinoma cells were injected into Rag−/− mice and the mice ...
Due to the important role of monocytes/macrophages in the pathogenesis of AIDS, potential drugs with anti-HIV activity in lymphocytes must also be effective in monocytes/macrophages. For testing the efficacy of antiviral substances, monocytes/macrophages from peripheral blood were infected, respectively, with highly replicating HIV1 and HIV2 strains, thereby providing an extremely sensitive system of testing. Azidothymidine was found to inhibit both HIV types at 0.04 microgram/ml. The polysulphated polyxylan, Hoe/Bay-946 (MW 6,000 Daltons), which acts through a different mechanism and is being tested in clinical pilot studies in Germany, was also found to be effective against HIV1 and HIV2 in macrophages at concentrations of 10-50 micrograms/ml. ...
Macrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers. IL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles
Salmonella induces programmed cell death in macrophages by complex mechanisms that involve distinct pathways and require the bacterial TTSS encoded in the pathogenicity island 1 (SPI-1 TTSS). One death pathway, which results in rapid macrophage death with features of necrosis, is dependent on caspase-1 and the SPI-1 TTSS-secreted protein SipB (Hersh et al., 1999; Brennan and Cookson, 2000; Jesenberger et al., 2000). However, macrophages from caspase-1−/− mice also undergo programmed cell death, although with delayed kinetics and different morphological features. Here, we have described another death pathway induced by Salmonella that is independent of caspase-1. A systematic bacterial genetic analysis led us to conclude that this cell death pathway is also dependent on SipB, a protein with membrane fusion activity that is delivered into host cells by the SPI-1 TTSS. This analysis was complicated by the known dual function of SipB, which acts both as an effector of virulence within cells and ...
Results Patients with lupus display decreased expression of Bim in circulating monocytes and reduced Bim expression in kidney macrophages. CreLysMBimflox/flox mice develop a lupus-like disease that mirrors aged Bim-/- mice including loss of the marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies including anti-DNA IgG, and a type I interferon signature as compared to control mice. CreLysMBimflox/flox mice also exhibit increased mortality attributed to immune complex deposition and increased numbers of kidney macrophages all of which contribute to glomerulonephritis. The loss of Bim in macrophages is sufficient to break tolerance as adoptive transfer of wild-type lymphocytes into CreLysMBimflox/floxRag-/- mice leads to systemic autoimmunity. We also identified that the loss of TLR signalling adaptor protein TRIF but not MyD88 is essential for progression to GN phase but is dispensable for systemic autoimmunity. RNA seq analysis of sorted kidney macrophages revealed a novel ...
Results In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206+ and IL-10+ TAMs at the tumour-stroma interface. ...
The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM(3)CSK(4). JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b(+) cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, ...
The diverse functions of macrophages as participants in innate and acquired immune responses are regulated by the specific milieu of environmental factors, cytokines, and other signaling molecules that are encountered at sites of inflammation. Microarray analysis of the transcriptional response of mouse peritoneal macrophages to the T(H)2 cytokine interleukin-4 (IL-4) identified Ym1 and arginase as the most highly up-regulated genes, exhibiting more than 68- and 88-fold induction, respectively. Molecular characterization of the Ym1 promoter in transfected epithelial and macrophage cell lines revealed the presence of multiple signal transducers and activators of transcription 6 (STAT6) response elements that function in a combinatorial manner to mediate transcriptional responses to IL-4. The participation of STAT6 as an obligate component of protein complexes binding to these sites was established by analysis of nuclear extracts derived from STAT6-deficient macrophages. Macrophage expression of Ym1 was
Macrophages have been found to both promote liver fibrosis and contribute to its resolution by acquiring different phenotypes based on signals from the micro-environment. The best-characterized phenotypes in the macrophage spectrum are labeled M1 (classically activated) and M2 (alternatively activated). Until now the in situ localization of these phenotypes in diseased livers is poorly described. In this study, we therefore aimed to localize and quantify M1- and M2-dominant macrophages in diseased mouse and human livers. The scarred collagen-rich areas in cirrhotic human livers and in CCl4-damaged mouse livers contained many macrophages. Though total numbers of macrophages were higher in fibrotic livers, the number of parenchymal CD68-positive macrophages was significantly lower as compared to normal. Scar-associated macrophages were further characterized as either M1-dominant (IRF-5 and interleukin-12) or M2-dominant (CD206, transglutaminase-2, and YM-1) and significantly higher numbers of both of
Regularly, we identified that host macrophages engulfed alloreactive T cells in between and h of in vitro culture and, as a result, way more effectively than host DC . To examine regardless of whether host macrophages may also engulf donor T cells in vivo, we traced the fate of alloreactive T cells for the duration of the h just after their injection in lethally irradiated recipient mice. Alloreactive T cells accumulated close to the spleen marginal zone shortly after adoptive transfer and steadily shifted toward the T cell area . A substantial amount of donor T cells had been trapped in the red pulp in close contact with host macrophages at early time points after their transfer . Steady with effects obtained in cultures, CFSE labeled donor T cells have been engulfed by splenic macrophages in the course of the 1st day of transplant and ahead of the initiation of donor T cell proliferation in vivo ...
The derivation of human macrophages from peripheral blood monocytes remains a convenient method for the study of macrophage biology. However, for macrophage differentiation, a significant proportion of development has occurred prior to the monocyte stage; monocyte subsets also have varying potential for differentiation. Differentiation of macrophages from a less mature precursor, such as CD34+ haematopoietic stem cells, can further inform with regard to the development of macrophage-lineage cells. CD34+ cells were cultured in serum-free medium containing Flt3L, SCF, IL-3, IL-6 and M-CSF. Using differing combinations of growth factors, the effect on cell proliferation and differentiation to adherent macrophage-like cells was determined. The proliferative response of CD34+ cells to M-CSF was determined during the initial phase of cell culture. Thirteen combinations of SCF, IL-3, IL-6 and M-CSF were then compared to determine the optimum combination for proliferation. Adherence was used to isolate mature
Mouse monoclonal antibody raised against macrophage surface antigen. Native human alveolar macrophages. (MAB1733) - Products - Abnova
Myocardial healing after myocardial infarction (MI) is accomplished by replacement fibrosis in the damaged region, and interstitial fibrosis takes place in the remote areas toward adverse ventricular remodeling. The collagen is produced by myofibroblasts, with infiltrating macrophages further facilitating this process (1,2). Macrophages infiltrate in large numbers at the site of injury after MI in human and in experimental animal models (3). These macrophages aid in the process of myocardial healing and assume multiple roles at different stages, depending on their origin whether infiltrating or resident (3,4). This involves removal of dead necrotic and apoptotic cells, regulation of fibroblast/myofibroblast function, and ultimately, wound resolution. Macrophages and fibroblasts are 2 major cell types involved in myocardium healing, and often lead to adverse myocardial remodeling and fibrosis (1,2,5).. It is well established that differentiated cells in various circumstances change their ...
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about 21 micrometres (0.00083 in) in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals. Their role is to phagocytose (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens. They are specialized phagocytic cells that attack foreign substances, infectious Microbes and cancer cells through destruction and ingestion. Macrophages can be identified by specific expression of a number of proteins including CD14, CD11b, F4/80 (mice)/EMR1 (human), Lysozyme M, MAC-1/MAC-3 and CD68 by flow cytometry or immunohistochemical staining. They move by action of Amoeboid movement.
Lung macrophages (LMϕs) play a key role in pulmonary innate immunity. They polarize into different phenotypes adapting to the needs of the immediate pulmonary environment. Studies in our laboratory suggest that murine LMϕs are endowed with an autocrine gamma-aminobutyric acid (GABA) signaling system. My honors thesis study found that antagonizing the autocrine GABA signaling in alveolar macrophages (AMϕs) increased secretion of the M1 cytokine tumor necrosis factor-alpha (TNF-α), suggesting a role for GABA signaling in immune response. This project explored whether GABA signaling plays a role in LMϕ polarization. Results from this study confirmed that bacterial toxin lipopolysaccharide (LPS) and the Th1 cytokine interferon gamma (IFNγ) shifted LMϕs to the pro-inflammatory M1 phenotype, marked by increased expression of inducible nitric oxide synthase (iNOS). On the other hand, the Th2 cytokines interleukin (IL)-4 and IL-13 shifted LMϕs toward the M2 phenotype marked by increased arginase-1.
TY - JOUR. T1 - Intrinsic and extrinsic factors in muscle aging. AU - Cannon, Joseph G.. PY - 1998/1/1. Y1 - 1998/1/1. N2 - The regenerative potential of skeletal muscle, and overall muscle mass, decline with age. This regenerative potential may be influenced by autocrine growth factors intrinsic to the muscle itself. Extrinsic host factors that may influence muscle regeneration include hormones, growth factors secreted in a paracrine manner by accessory cells, innervation, and antioxidant mechanisms. Unaccustomed exercise, which involves mechanical overload of myofibers, provides a convenient method for studying muscle regeneration in both humans and animal models. An inflammatory response ensues in which distinctive populations of macrophages infiltrate the affected tissue: some of these macrophages are involved in phagocytosis of damaged fibers; other macrophages arriving at later times may deliver growth factors or cytokines that promote regeneration. These include fibroblast growth factor ...
Monocytes, macrophages and dendritic cells (DCs) are developmentally related regulators of the immune system that share the monocyte-macrophage DC progenitor (MDP) as a common precursor. Unlike differentiation into DCs, the distal pathways for differentiation into monocytes and monocyte-derived macrophages are not fully elucidated. We have now demonstrated the existence of a clonogenic, monocyte- and macrophage-restricted progenitor cell derived from the MDP. This progenitor was a Ly6C+ proliferating cell present in the bone marrow and spleen that generated the major monocyte subsets and macrophages, but not DCs or neutrophils. By in-depth quantitative proteomics, we characterized changes in the proteome during monocyte differentiation, which provided insight into the molecular principles of developing monocytes, such as their functional maturation. Thus, we found that monocytes and macrophages were renewed independently of DCs from a committed progenitor ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
In this study, we sought to determine whether CX3CL1 and CCR2 act independently or in concert to promote lesion formation through their effects on macrophage accumulation. There are 2 major findings in the present study. First, although deletion of either CX3CL1 or CCR2 reduced macrophage presence and atherosclerosis, atheroprotection in the CCR2−/− mice was more robust. Second, there was an even greater reduction of lesion formation in the CX3CL1−/− CCR2−/− double knockouts, which suggests that CX3CL1 and CCR2 have independent functions in recruiting monocyte/macrophages. These differences, which were not linked to changes in cholesterol levels or lipoprotein profiles, provide mechanistic insights into the role of monocyte chemoattractants in fatty streak formation and early plaque development.. The past 2 decades have witnessed a rapid increase in our understanding of leukocyte migration throughout the body, with the identification of ≈50 chemokines and ,20 chemokine receptors. ...
RNA interference is an evolutionary conserved immune response mechanism that can be used as a tool to provide novel insights into gene function and structure. The ability to efficiently deliver small interfering RNA to modulate gene expression in vivo may provide new therapeutic approaches to currently intractable diseases. In vitro, siRNA targeting IL-12p40 was delivered to the murine macrophage cell line (J774A.1) encapsulated in a liposome with an IL-12 inducing agent (LPS/IFN-γ) over a number of time points. Controls included a variety of non-target specific siRNA reagents. Supernatants were analyzed for cytokine production while the cells were removed for mRNA profiling. In vivo, siRNA-targeting IL-12p40 was delivered to the murine peritoneal cavity in a therapeutic fashion, after endotoxin (LPS) challenge. Cells from the peritoneal cavity were removed by lavage and analyzed by flow cytometry. Levels of IL-12 present in lavage and in serum were also examined by ELISA. In this report, we show that
Persistent, unresolved inflammation in the liver represents a key trigger for hepatic injury and fibrosis in various liver diseases and is controlled by classically activated proinflammatory macrophages, while restorative macrophages of the liver are capable of reversing inflammation once the injury trigger ceases. Here we exhibit neutrophils as key contributors to resolving the inflammatory response in the liver using two models of liver inflammation resolution. Using two models of liver inflammatory resolution, we found that mice undergoing neutrophil depletion during the resolution phase exhibited unresolved hepatic inflammation, activation of the fibrogenic machinery, and early fibrosis. These findings were associated with an impairment of the phenotypic switch of proinflammatory macrophages into a restorative stage after removal of the cause of injury and an increased NLRP3/miR-223 ratio. Mice with a deletion of the granulocyte-specific miR-223 gene showed a similarly impaired resolution ...
...For those coping with Crohns disease a new research report published... By increasing the knowledge on the different macrophage subsets in th...To make this discovery scientists studied blood and intestinal biopsy...,Scientists,discover,the,specific,types,of,macrophages,that,affect,Crohns,disease,severity,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
A free platform for explaining your research in plain language, and managing how you communicate around it - so you can understand how best to increase its impact.
TY - JOUR. T1 - Intracellular bacteria recognition contributes to maximal interleukin (IL)-12 production by IL-10-deficient macrophages. AU - Naruse, H.. AU - Hisamatsu, T.. AU - Yamauchi, Y.. AU - Chang, J. E.. AU - Matsuoka, K.. AU - Kitazume, M. T.. AU - Arai, K.. AU - Ando, S.. AU - Kanai, Takanori. AU - Kamada, N.. AU - Hibi, T.. PY - 2011/4. Y1 - 2011/4. N2 - Interleukin (IL)-12 is a key factor that induces T helper cell type 1-mediated immunity and inflammatory diseases. In some colitis models, such as IL-10 knock-out (KO) mice, IL-12 triggers intestinal inflammation. An abundant amount of IL-12 is produced by intestinal macrophages in response to stimulation by commensal bacteria in IL-10 KO mice. Intact bacteria are more potent inducers of macrophage IL-12 production than cell surface components in this model. This suggested that cell surface receptor signalling and intracellular pathogen recognition mechanisms are important for the induction of IL-12. We addressed the importance of ...
Definition of macrophage colony stimulating factor in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is macrophage colony stimulating factor? Meaning of macrophage colony stimulating factor as a legal term. What does macrophage colony stimulating factor mean in law?
There are comments on PubPeer for publication: In vitro -induced M2 type macrophages induces the resistance of prostate cancer cells to cytotoxic action of NK cells (2018)
Background Estimating the mandatory dose in radiotherapy can be of crucial importance because the administrated dose ought to be sufficient to eliminate the tumor and at the same time should inflict minimal harm on normal cells. Outcomes We derive a precise phase-diagram for the steady-state TCP from the display and model that at high, clinically-relevant dosages of rays, the differentiation between energetic and quiescent tumor cells (i.e. accounting for cell-cycle Mouse monoclonal antibody to TAB1. The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinaseMAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such asthose induced by TGF beta, interleukin 1, and WNT-1. This protein interacts and thus activatesTAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for bindingand activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor ofTGF beta, suggesting that this ...
Macrophages. Coloured scanning electron micrograph (SEM) of active macrophage cells. In the active state the cell surfaces appear frilly and these frills spread out as projections to draw the cells along the substrate as they seek and engulf particles. Wandering macrophages are monocyte white blood cells from circulating blood that defend the body against invasion by foreign organisms. Macrophages migrate to tissues such as the lymphatic system and lungs. Some types migrate to sites of infection to prevent bacteria taking hold. Macrophages can also detect foreign subst- ances at the initial stage of the bodys immune response. Magnification: x1,500 at 6x7cm size. x5000 at 8x10 inch size. - Stock Image P276/0132
Macrophages are mononuclear phagocytes that play a central role in tissue development and homeostasis, and protecting the organism from infection. Our laboratory is interested in describing the properties of tissue-resident human macrophages and how their properties change throughout life, using modern technologies such as advanced flow cytometry and single cell RNA sequencing. This project aims to describe the properties of placental macrophages and the role they play in anti-viral fetal defense.. Recent Publications. McGovern N, Shin A, Low G, Low D, Duan K, Yao LJ, Msallam R, Low I, Shadan NB, Sumatoh HR, Soon E, Lum J, Mok E, Hubert S, See P, Kunxiang EH, Lee YH, Janela B, Choolani M, Mattar CNZ, Fan Y, Lim TKH, Chan DKH, Tan KK, Tam JKC, Schuster C, Elbe-Bürger A, Wang XN, Bigley V, Collin M, Haniffa M, Schlitzer A, Poidinger M, Albani S, Larbi A, Newell EW, Chan JKY, Ginhoux F. Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2. Nature. 2017 Jun ...
In this study, the human leukemic monocyte lymphoma cell line U-937 was used as an in vitro model for monitoring monocyte/macrophage differentiation. Phorbol 12- myristate (13) (PMA) was used to activate U-937 cells into macrophage-like cells (M0). After 24 hours of PMA treatment, non- adherent U-937 cells became tightly adherent to the culture plates forming M0 cells. M0 cells were then polarized into the M1 macrophage phenotype by treatment with LPS and IFN-γ for another 24 hours. Each of the cytokines IL-4, IL-13, or IL-10 was applied separately to three M0 cultures for 24 hours to induce the M2 macrophage phenotype. M1 and M2 phenotypes displayed distinct morphological characteristics. M1 cells appeared large, with cellular processes (pseudopodia), and intracellular vacuoles while the M2 cells large aggregated into large masses. The undifferentiated U--937 cells expressed less CD206 and CD86 but greater amounts of CD163, CD80, and CD200R than did the differentiated U937 cells (M0 macrophages).
Schroit, A; Geiger, B; and Gallily, R, "The capacity of macrophage components to inhibit anti-macrophage serum activity." (1973). Subject Strain Bibliography 1973. 2291 ...
Despite the extensive studies in the past two decades and the development of a generic cell migration model, composed of cell adhesion, detachment, and receptor recycling (Stossel, 1994; Murphy and Gavrilovic, 1999; Sanchez‐Madrid and del Pozo, 1999; Webb et al, 2002), the extracellular events that orchestrate temporally and spatially the transition among these individual steps are unknown. Moreover, evidence for a critical role of macrophage emigration to the lymph nodes in inhibiting the progression of atherosclerosis is emerging (Libby, 2002; Llodra et al, 2004). However, the mechanism that controls their emigration, especially under activated conditions, remains elusive. In this work, we explored the mechanism by which activated macrophages migrate within an inflammatory environment using genetic and biochemical approaches. Our data reveal that deletion of the PAI‐1, tPA, LRP, and Mac‐1 genes all impair the ability of macrophages to migrate from the peritoneal cavity in response to ...
Macrophages play an important role in immune and non-immune defence mechanisms. They form a first line of defence against bacterial, viral and other forms of microbiological contamination penetrating into the bodies of vertebrates. Macrophages are large cells, found in almost all bodily tissues where they can have varying forms and names (e.g. Kupffer cells, alveolar macrophages, microglia, osteoclasts, red pulp macrophages). Macrophages "scavenge", they ingest and digest all foreign substances, microbes, cancer cells and cellular debris that might be potential pathogens. This process is called phagocytosis. Macrophages further regulate functions of many non-phagocytic cells, mainly through mediation of soluble molecules such as cytokines and chemokines. They are involved in innate immunity, adaptive immunity and can have (anti-) inflammatory effects.. Liposomes are artificially prepared spheres and consist of concentric phospholipid bilayers. When phospholipids are dispersed in water, the ...
The most abundant immune cell types of the tumor microenvironment macrophages recruited there by tumor-eluted factors. The role of these immune cells in tumor progression, and the interplay between tumor and immune cells is an emerging field of research with potential for novel treatment strategies. Here, a TIE2 expressing macrophage (TEM) subtype is integrated into a virtual tumor model. Within the 2D microenvironment, the TEM will differentiate from an extravasated monocyte precursor, congregate around the abluminal side of the vasculature in response to a chemoattractant gradient, secrete cytokines which favor differentiation of a separate angiogenic macrophage subtype [1]. The effects of macrophage populations on tumor progression on angiogenic activity and tumor growth will be examined.
AFIK we do not know exactly why activated macrophages express substantially increased FR beta receptors. This is further complicated by the notion of polarized macrophages as well as a number of different macrophage phenotypes (which can be changed by signaling from one the same macrophage) that are considered proinflammatory and anti inflammatory. I have questioned experts in the field since I am working on a folate receptor conjugate that can be used to externally image macrophages in atheroma , potentially stratifying fibrous from vulnerable plaques. They do not know why FR beta is expressed or whether someone on folate supplemation is exacerbating or reducing risk. Cold folate will partially block the affinity of receptors for conjugated folate used in imaging. However, FR beta is considered a Trojan horse for the introduction of drugs for diagnosis and therapy of macrophage laden plaques. The kind that want to cause big trouble. I read that folate also affects the production of ROS in ...
AFIK we do not know exactly why activated macrophages express substantially increased FR beta receptors. This is further complicated by the notion of polarized macrophages as well as a number of different macrophage phenotypes (which can be changed by signaling from one the same macrophage) that are considered proinflammatory and anti inflammatory. I have questioned experts in the field since I am working on a folate receptor conjugate that can be used to externally image macrophages in atheroma , potentially stratifying fibrous from vulnerable plaques. They do not know why FR beta is expressed or whether someone on folate supplemation is exacerbating or reducing risk. Cold folate will partially block the affinity of receptors for conjugated folate used in imaging. However, FR beta is considered a Trojan horse for the introduction of drugs for diagnosis and therapy of macrophage laden plaques. The kind that want to cause big trouble. I read that folate also affects the production of ROS in ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and ...
A recent study proposes a novel role for inhibitory guidance cues in regulating macrophage trafficking during atherosclerosis.1 The study authors demonstrate that Netrin-1, a laminin-related protein with a previously established role in axon migration and tumorigenesis, contributes to atherosclerosis by preventing the emigration of macrophages from plaque.. Monocyte recruitment to areas of subendothelial lipid deposition has long been identified as a critical early step in the inflammatory pathophysiology of atherosclerosis.2,3 Less is known, however, about the signals that mediate both the retention and efflux of macrophages from atherosclerotic lesions. Evidence from prior studies has suggested that lipid accumulation promotes the retention of macrophages in atherosclerotic lesions by disrupting CCR7-dependent chemotaxis, which under normal conditions enhances macrophage efflux from sites of inflammation.4-6 Other studies have shown that inhibitory guidance cues mediated by the laminin-related ...
Macrophage engulfing bacteria http://bit.ly/1HAcwgY Macrophages are a type of white blood cells essential for the human immune system to protect the body against foreign substances such as virus and bacteria. They also play a crucial role in tissue homeostasis and can contribute to tumor growth and chronic inflammatory diseases such as diabetes, obesity etc. Macrophages are therefore potential drug targets and there is a growing interest in understanding these white blood cells.. The prevailing dogma states that macrophages are produced from monocytes generated in the bone marrow from adult hematopoietic stem cells. However, scientists from the Singapore Immunology Network (SIgN), a research institute under the Agency for Science, Technology and Research (A*STAR), Singapore have shed some light on the origin of adult tissue macrophages. The work was published in the prestigious scientific journal Immunity.. A team of scientists led by Dr. Florent Ginhoux, Principal Investigator of SIgN, ...
Macrophages make an antiviral protein called SAMHD1, which prevents HIV from replicating in these cells - except for when the protein is switched off, as part of a natural process discovered by the UCL-led team.. "We knew that SAMHD1 is switched off when cells multiply, but macrophages do not multiply so it seemed unlikely that SAMHD1 would be switched off in these cells," said Professor Ravindra Gupta (UCL Infection & Immunity), the senior author of the paper. "And yet we found theres a window of opportunity when SAMHD1 is disabled as part of a regularly-occurring process in macrophages.". Lead author of the EMBO Journal study, Dr Petra Mlcochova (UCL Infection & Immunity) said: "Other viruses can disable SAMHD1, but HIV cannot. Our work explains how HIV can still infect macrophages, which are disabling SAMHD1 by themselves.". The reason why SAMHD1 gets switched off remains to be determined, but the authors suggest it might be done in order to repair damaged DNA, part of the normal functioning ...
The global burden of chronic kidney diseases remains an ongoing medical challenge. Therapies that can halt or reverse advanced renal injury are not yet available. Increasing numbers of patients progress to the end-stage renal failure and require renal replacement therapy, the latter being associated with significant mortality, a lower quality of life, and high costs for national health systems. Thus, new treatment strategies that slow down, halt or even revert progressive renal damage are requested. Chemokines and their receptors are involved in the pathogenesis of renal diseases. They mediate leukocytes and macrophages recruitment and activation during initiation as well as progression of renal inflammation. Infiltrating leukocytes are the major source for proinflammatory and profibrotic cytokines and are therefore critical for mediating fibroblast proliferation, differentiation into myofibroblasts, matrix production, and tubular atrophy. Recent advances in the understanding of the molecular ...
People with diabetes are at increased risk for atherosclerosis and have high CVD morbidity and mortality rates. Tools for detecting and quantifying atherosclerotic pro/regression in people with diabetes and other CVD risk factors lack sensitivity and specificity for molecular level events that occur during the early stages of atherogenesis. Inflammatory macrophage infiltration in the vessel endothelium is an early, molecular level proatherogenic event. Activated macrophages consume glucose at a high rate. Novel in vivo radiotracer PET/CT techniques have been developed to detect, image and quantify molecular level events like macrophage inflammation and glucose utilization (18FDG) in human vessels. We propose to develop and test this novel technique in the Center for Clinical Imaging Research (CCIR) at WUMS. We propose that HIV-infected people with significant CVD risk profiles are a suitable, unique human model for testing these novel imaging techniques. HIV-infected people taking anti-HIV ...
Integrative genomics gets the potential to discover relevant loci, as scientific outcome and response to chemotherapies are likely not because of an individual gene (or data type) but instead a complicated relationship involving hereditary variation, mRNA, DNA methylation, and duplicate number variation. the knockdown of and led to CDDP level of resistance in multiple cancers cell lines. This research demonstrates the tool of the integrative GS evaluation strategy for discovering novel genes connected with response to cancers therapies, moving nearer to customized therapy decisions for cancers patients. Launch Platinum agents, such as for example cisplatin (CDDP), are generally used in the treating a number of malignancies, including ovarian and lung malignancies. Nevertheless, response to therapy varies among sufferers. One of the primary challenges to attain desirable therapeutic results is the huge inter-patient deviation in scientific response and toxicity. Main molecular mechanisms root ...
Macrophage polarization review exploring the function and phenotype of M1, M2, TAM, TCR+, CD169+ macrophages, plus comparisons between mouse and human macrophages
This necessity for prolonged contact may prove to be important for macrophage activation. This is suggested by comparing the prolonged effects in vivo of injection of casein, on the one hand, and C. parvum or other anaerobic coryneforms on the other. Both have short-term stimulating effects on macrophages. Both casein and C. parvum are chemotactic for macrophages and both induce a macrophage exudate 2-5 days after injection into the peritoneal cavity of the guinea-pig (49). However after casein-induction, these macrophages disappear from the peritoneal cavity soon afterwards. The relevance of this mechanism to the microbicidal effect of activated macrophages is not known, especially since mature macrophages, at least in the mouse, are thought to be relatively poor in peroxidase activity (25). 2. Nonmicrobial Targets Activated macrophages appear to kill tumor cells by a nonphagocytic mechanism. Several authors have emphasized the need for a close contact between activated macrophages and target ...
The Institute of Pharmacology and Structural Biology (www.ipbs.fr) has an open postdoctoral position to work on podosomes, cell structures involved in adhesion, matrix proteolysis, mechanosensing and cell migration in 3D environments (1-9). Macrophage tissue infiltration plays beneficial roles in protective immunity and detrimental roles in several diseases. Tissue infiltrated macrophages favor the progression of e.g. most cancers and chronic inflammations. Therefore, it is a challenging issue to control macrophage migration as a new therapeutic strategy.. Our team has reported that podosomes are instrumental in the protease-dependent 3D migration of macrophages. To progress in the knowledge of this cell structure, we developed a method called Protrusion Force Microscopy (3,10,11) and we used STORM-SAF microscopy (12) that allowed drawing a preliminary picture of the podosome architecture which explains the generation of protrusive force (13). Now, we plan to further characterize the ...
Introduction Methotrexate (MTX) induces macrophage apoptosis in vitro, but there is not much evidence for increased synovial macrophage apoptosis in MTX-treated patients. Macrophage apoptosis is...
In HIV-infected macrophages, newly formed progeny virus particles accumulate in intracellular plasma membrane-connected compartments (IPMCs). Although the virus is usually seen in these compartments, it is unclear whether HIV assembly is specifically targeted to IPMCs or whether some viruses may also form at the cell surface but are not detected, as particles budding from the latter site will be released into the medium. To investigate the fidelity of HIV-1 targeting to IPMCs compared to the cell surface directly, we generated mutants defective in recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) proteins required for virus scission. For mutants unable to bind the ESCRT-I component Tsg101, HIV release was inhibited and light and electron microscopy revealed that budding was arrested. When expressed in human monocyte-derived macrophages (MDM), these mutants formed budding-arrested, immature particles at their assembly sites, allowing us to capture virtually all of the virus
Sigma-Aldrich offers abstracts and full-text articles by [Simone Merlin, Kuldeep K Bhargava, Gabriella Ranaldo, Diego Zanolini, Christopher J Palestro, Laura Santambrogio, Maria Prat, Antonia Follenzi, Sanjeev Gupta].
Large collection of high quality biology pictures, photos, images, illustrations, diagrams and posters on marine biology, cell biology, microbiology... for educational purposes.. ...
Materials and methods Cultures of human THP-1 were activated to macrophages by interferon γ (IFNγ) (500 U/ml) and treated for 24 h with calcitriol (10−8M) and 17β-estradiol (E2, 10−8M) alone and in combination.Untreated macrophages (THP-1-activated) were used as controls (cnt). P450-aromatase synthesis was evaluated by immunocytochemistry (ICC) and western blotting (WB), whereas the expression of the related CYP19A1 gene was quantified by Real-Time PCR (RT-PCR). IL-1β, IL-6 and TNFα synthesis was analysed by enzyme immunoassay (ELISA) and WB. The signal transduction pathway of mitogen activated proteins ERK1/2 was evaluated by WB.. ...
Macrophages are major constituents of the microenvironment in many cancers, promoting carcinogenesis, malignant progression and resistance to therapy making them attractive targets for therapeutic intervention. Macrophage Pharmas approach is to manipulate tumour associated macrophages to inhibit the immunosuppression that they generate, leading to more effective anti-tumour immune responses. Esterase Sensitive Motif™ technology represents a strategy of highly selective delivery of small molecule inhibitors to tumour macrophages such that the function of other important anti-tumour immune cells is not impacted. Macrophage Pharma believes that development of these highly novel therapeutics will lead to optimal anti-tumour macrophage activities providing maximal therapeutic responses.. ...
Definition of macrophage processing in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is macrophage processing? Meaning of macrophage processing as a finance term. What does macrophage processing mean in finance?