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*  Characterization of foam cell formation in human macrophage subsets (95.17) | The Journal of Immunology
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 ...
  http://www.jimmunol.org/content/178/1_Supplement/S180.2
*  Abstract 520: High-density Lipoprotein Inhibits Human M1 Macrophage Polarisation through the Redistribution of Caveolin-1 |...
Macrophages play a critical role in the development and progression of atherosclerosis. Depending on their surrounding milieu, macrophages can adopt a wide range of functional phenotypes; pro-inflammatory (M1) and pro-resolving (M2). HDL has many cardio-protective properties including potent anti-inflammatory effects, largely through the removal of cholesterol from cells. It is currently not known if this extends to influencing human macrophage phenotypes. Thus, we aimed to investigate the effect of HDL on human macrophage polarisation. Human blood monocyte-derived macrophages were induced to either an M1-phenotype by incubation with LPS and IFN-γ or to an M2-phenotype with IL-4. Macrophages were differentiated in the presence or absence of human HDL and their phenotypes were characterised using cell surface markers, reactive oxygen species (ROS) production by flow cytometry, and mRNA expression by real-time PCR. Downstream signalling ...
  http://atvb.ahajournals.org/content/35/Suppl_1/A520
*  Perivascular Macrophages Are the Primary Cell Type Productively Infected by Simian Immunodeficiency Virus in the Brains of...
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 ...
  http://jem.rupress.org/content/193/8/905
*  Increased susceptibility to activation and increased uptake of low density lipoprotein by cholesterol-loaded 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 ...
  http://atvb.ahajournals.org/content/12/6/745
*  Thioglycollate-elicited murine macrophages are cytotoxic to Mycoplasma arginini-infected YAC-1 tumor cells
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 ...
  http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1998001100010&lng=en&nrm=iso&tlng=en
*  In vitro Analysis for Macrophage Binding and Pro-inflammatory Responses to Candida albicans -BIO-PROTOCOL
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
  http://www.bio-protocol.org/e1123
*  MicroRNAs in Immune Response and Macrophage Polarization | Arteriosclerosis, Thrombosis, and Vascular Biology
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 ...
  http://atvb.ahajournals.org/content/33/2/170.full
*  Tumor-associated macrophage - Wikipedia
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 ...
  https://en.wikipedia.org/wiki/Tumor-associated_macrophage
*  Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages. | JEM
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 ...
  http://jem.rupress.org/content/152/5/1248
*  Adipose Fatty Acid Binding Protein Promotes Saturated Fatty Acid-Induced Macrophage Cell Death through Enhancing Ceramide...
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 ...
  http://www.jimmunol.org/content/198/2/798
*  Human bronchoalveolar macrophage heterogeneity demonstrated by histochemistry, surface markers and phagocytosis. - Semantic...
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 ...
  https://www.semanticscholar.org/paper/Human-bronchoalveolar-macrophage-heterogeneity-dem-Gant-Hamblin/072e73426b9a70a1e605dbbd95e88d5da41696f4
*  Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a...
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 ...
  http://eprints.nottingham.ac.uk/40797/
*  Early Macrophage Recruitment and Alternative Activation Are Critical for the Later Development of Hypoxia-Induced Pulmonary...
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 ...
  http://circ.ahajournals.org/content/123/18/1986
*  Switching Macrophage Responses | Science Signaling
Macrophages exist in at least two functionally distinct states that are triggered in response to different stimuli: M1 macrophages are involved in proinflammatory responses [characterized by proinflammatory cytokine release, such as interleukin-1β (IL-1β), and production of reactive oxygen species (ROS)], and M2 macrophages are involved in resolution of inflammation (characterized by production of scavenger receptors and IL-1 receptor antagonist, and decreased production of proinflammatory cytokines, including IL-1β). To better understand these differences in macrophage functional states, Pelegrin and Surprenant developed an in vitro protocol that allowed them to define five different macrophage states from M1 through M2, with state 1 corresponding to M1 cells, state 5 corresponding to M2 cells, and state 3 corresponding to cells equally intermediate between M1 and M2 (M1/M2 cells). With these five-state cells, they showed that M1 cells responded to ...
  http://stke.sciencemag.org/content/2/81/ec252
*  Genetic background affects the expansion of macrophage subsets in the lungs of Mycobacterium tuberculosis-infected hosts. -...
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 ...
  https://www.semanticscholar.org/paper/Genetic-background-affects-the-expansion-of-macrop-Bertolini-Souza/33d5d9d4835966ee79be57dd902912680fbcad46
*  Macrophages Kill T9 Glioma Tumor Cells Bearing the Membrane Isoform of Macrophage Colony Stimulating Factor Through a...
Macrophages can be considered a "double edged sword" in tumor biology; these cells are commonly found within various tumors in response to M-CSF produced by these tumors (22, 23, 24, 25, 26). Macrophages stimulate tumor growth by releasing growth or angiogenic factors or by acting as immunosuppressor cells (34, 35, 36, 37, 38, 39). Other studies concluded that macrophages were beneficial for the host's survival (40, 41, 42, 43, 44, 45). For macrophages to become tumoricidal in vitro they must be stimulated twice (5, 6). First, cytokines prime the macrophages, while secondary signals allow the macrophage to kill the tumor cell. It could be speculated that this "double edged sword" effect is explainable by the two-signal model. When macrophages receive the priming signal, they promote tumor growth and metastases. Whereas, when both signals are received the macrophages mediate tumor regression. ...
  http://www.jimmunol.org/content/160/1/361.long
*  "Comparison of Different Modulators that Affect Macrophage Activation I" by Alda Alexa Díaz Pérez
Inflammation is known as a mechanism to regulate and control infections as well as promote tissue repair. Macrophages (Mф) are known to be a major cell type in the initiation, sustainability and resolution of inflammation. Moreover, Mф are essential for the remodeling process that is also known as the wound healing response. The objective of this research was to compare five modulators (acetylsalicylic acid (ASA), dexamethasone (DEX), prostaglandin E2 (PGE2), iloprost, and resolvin D1 (RvD1) for their anti-inflammatory effects on macrophages in vitro. Then, Mф phenotype in terms of gene expression and secreted cytokine response was determined. Our study compared NR8383 cells induced with LPS versus a modulator. Using ELISA measurements of chemokine (C-C motif) ligand 2 (CCL2), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α) performed. Gene expression analysis for the following transcripts: arginase -2 (ARG-2), nitric oxide synthesis type ...
  http://scholarworks.uark.edu/etd/1279/
*  Glass, C.K. (2001) Potential roles of the peroxisome proliferator-activated receptorγ in macrophage biology and atherosclerosis...
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
  http://www.scirp.org/reference/ReferencesPapers.aspx?ReferenceID=520967
*  The Exonuclease Trex1 Restrains Macrophage Proinflammatory Activation | The Journal of Immunology
The three-prime repair exonuclease 1 (TREX1) is the most abundant exonuclease in mammalian cells. Mutations in Trex1 gene are being linked to the development of Aicardi-Goutières syndrome, an inflammatory disease of the brain, and systemic lupus erythematosus. In clinical cases and in a Trex1-deficient murine model, chronic production of type I IFN plays a pathogenic role. In this study, we demonstrate that Trex1−/− mice present inflammatory signatures in many different organs, including the brain. Trex1 is highly induced in macrophages in response to proinflammatory stimuli, including TLR7 and TLR9 ligands. Our findings show that, in the absence of Trex1, macrophages displayed an exacerbate proinflammatory response. More specifically, following proinflammatory stimulation, Trex1−/− macrophages exhibited an increased TNF-α and IFN-α production, higher levels of CD86, and increased Ag presentation to CD4+ T cells, as well as an impaired apoptotic T cell ...
  http://www.jimmunol.org/content/early/2013/11/08/jimmunol.1301603
*  "Differential response of macrophage subpopulations to soleus muscle re" by Barbara St. Pierre Schneider and James G. Tidball
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 ...
  https://digitalscholarship.unlv.edu/nursing_fac_articles/160/
*  Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses | The Journal of Immunology
Since the pioneering work of Elie Metchnikoff and the discovery of cellular immunity, the phagocytic clearance of cellular debris has been considered an integral component of resolving inflammation and restoring function of damaged and infected tissues. We now know that the phagocytic clearance of dying cells (efferocytosis), particularly by macrophages and other immune phagocytes, has profound consequences on innate and adaptive immune responses in inflamed tissues. These immunomodulatory effects result from an array of molecular signaling events between macrophages, dying cells, and other tissue-resident cells. In recent years, many of these molecular pathways have been identified and studied in the context of tissue inflammation, helping us better understand the relationship between efferocytosis and inflammation. We review specific types of efferocytosis-related signals that can impact macrophage immune responses and discuss their relevance to inflammation-related ...
  http://www.jimmunol.org/content/198/4/1387
*  MicroRNA-24 Regulates Macrophage Behavior and Retards AtherosclerosisSignificance | Arteriosclerosis, Thrombosis, and Vascular...
The interminable recruitment of inflammatory monocyte/macrophages and their associated increased proteolytic potential are considered pivotal to atherosclerotic lesion progression and rupture. In our current study, we demonstrate that perturbation of macrophage microRNA-24 heightens their proteolytic capacity and renders them proatherosclerotic. During M-CSF directed macrophage maturation, expression of microRNA-24 is essential for the downregulation of MMP-14 protein expression. However, GM-CSF matured macrophages exhibit retarded microRNA-24 levels, resulting in elevated MMP-14 activity and promoting a proinflammatory phenotype characterized as invasive and proapoptotic, but with reduced proliferative rates. Consequently, in vivo microRNA-24 inhibition augmented the progression of established atherosclerotic plaques associated with increased expression and activity of MMP-14 in intraplaque macrophages. In addition, plaque composition was altered and ...
  http://atvb.ahajournals.org/content/34/9/1990
*  Thiol Oxidative Stress Induced by Metabolic Disorders Amplifies Macrophage Chemotactic Responses and Accelerates Atherogenesis...
In this study we examined whether metabolic stress induced by hypercholesterolemia alone or hyperlipidemia plus hyperglycemia accelerates atherosclerosis and renal injury by promoting thiol oxidative stress in macrophages and increasing the recruitment of macrophages to sites of tissue injury. We found that with each additional level of metabolic stress, macrophage accumulation increased in both atherosclerotic lesions and in kidneys of LDL-R−/− mice. Analysis of the macrophage glutathione reduction potential (Eh) revealed that metabolic stress promotes intracellular thiol oxidation and that oxidation of the macrophage glutathione reduction state correlates with both accelerated macrophage recruitment and increased lesion severity. Macrophage recruitment into MCP-1-loaded Matrigel plugs implanted in these mice was also accelerated with each additional level of metabolic stress, suggesting that increased cellular thiol oxidation induced by metabolic stress amplifies ...
  http://atvb.ahajournals.org/content/29/11/1779
*  Murine macrophage behavior on peptide-grafted polyethyleneglycol-containing networks
Polyethyleneglycol-based networks were employed as substrates to graft bioactive peptides to study macrophage interactions with materials. Our overall objective was to utilize biologically active factors to stimulate certain macrophage function on materials suitable for implantation in connective tissues. In this study, we sought to explore the bioactivity of several peptides derived from extracellular matrix adhesion proteins and macrophage-active proteins that are normally soluble. The candidate peptides examined corresponded to residues 63 to 77 of complement component C3a (C3a(63-77)), residues 178 to 207 of interleukin-1 beta (IL1beta(178-207)), residues 1615 to 1624 of fibronectin (FN(1615-1624)), endothelial-macrophage activating polypeptide II, complement component C5a inhibitory sequence, macrophage inhibitory peptide, and YRGDG; materials lacking peptides were used as negative controls. An established murine cell-line IC-21 was employed as a macrophage model, and human dermal ...
  https://infoscience.epfl.ch/record/81232