Alternative Activation of Macrophages: An Immunologic Functional Perspective

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Annual Review of Immunology (Impact Factor: 39.33). 04/2009; 27(1):451-83. DOI: 10.1146/annurev.immunol.021908.132532
Source: PubMed


Macrophages are innate immune cells with well-established roles in the primary response to pathogens, but also in tissue homeostasis, coordination of the adaptive immune response, inflammation, resolution, and repair. These cells recognize danger signals through receptors capable of inducing specialized activation programs. The classically known macrophage activation is induced by IFN-gamma, which triggers a harsh proinflammatory response that is required to kill intracellular pathogens. Macrophages also undergo alternative activation by IL-4 and IL-13, which trigger a different phenotype that is important for the immune response to parasites. Here we review the cellular sources of these cytokines, receptor signaling pathways, and induced markers and gene signatures. We draw attention to discrepancies found between mouse and human models of alternative activation. The evidence for in vivo alternative activation of macrophages is also analyzed, with nematode infection as prototypic disease. Finally, we revisit the concept of macrophage activation in the context of the immune response.

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    • "Mediators of Inflammation that mediate the systemic inflammatory response syndrome (SIRS), whereas the " M2 " alternate macrophage responses are seen in the compensatory anti-inflammatory response syndrome (CARS), parasitic infections, tumor growth promotion , and healing [9]. M1 and M2 macrophage activation states have been described in detail [10] [11]. "
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    ABSTRACT: In a swine model of ischemia/reperfusion injury coupled with sepsis, we have previously shown attenuation of secondary organ injury and decreased mortality with negative pressure therapy (NPT). We hypothesized that NPT modulates the intestinal microenvironment by mediating the innate immune system. Sepsis was induced in 12 anesthetized female pigs. Group 1 (n = 6) was decompressed at 12 hrs after injury (T 12) and treated with standard of care (SOC), and group 2 (n = 6) with NPT for up to T 48. Immunoparalysis was evident as lymphocytopenia at T 24 in both groups; however, survival was improved in the NPT group versus SOC (Odds ratio = 4.0). The SOC group showed significant reduction in lymphocyte numbers compared to NPT group by T 48 (p < 0.05). The capacity of peritoneal fluid to stimulate a robust reactive oxygen species response in vitro was greater for the NPT group, peaking at T 24 for both M1 (p = 0.0197) and M2 macrophages (p = 0.085). Plasma elicited little if any effect which was confirmed by microarray analysis. In this septic swine model NPT appeared to modulate the intestinal microenvironment, facilitating an early robust, yet transient, host defense mediated by M1 and M2 macrophages. NPT may help overcome immunoparalysis that occurs during inflammatory response to septic injury.
    Mediators of Inflammation 08/2015; 2015(5):419841. DOI:10.1155/2015/419841 · 3.24 Impact Factor
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    • "BioMed Research International tissues, inhibit T-cell differentiation and functions, lower cytotoxic T-cell function, induce T-cell apoptosis, secrete CCL18, and attract na¨ıve T cell [10] [16] [32] [35]. Immune modulatory and antitumor effects of mushroom beta-glucan have been noted by Ikekawa et al. in 1968 in the fruiting body extracts of Lentinus edodes, Coriolus versicolor, Ganoderma tsugae, Flammulina velutipes, and Tricholoma matsutake which have demonstrated significant antitumor activities towards transplanted tumor cells of sarcoma 180 [36] [37] [38]. "
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    ABSTRACT: The present study showed that oral mushroom beta-glucan treatment significantly increased IFN-γ mRNA expression but significantly reduced COX-2 mRNA expression within the lung. For LLC tumor model, oral Ganoderma lucidum or Antrodia camphorata polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2, and TGF-β mRNA expression were substantially following oral mushroom polysaccharides treatments. The study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides.
    07/2015; 2015:604385. DOI:10.1155/2015/604385
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    • "This cytokine converts resting macrophages into potent cells with increased antigen presenting capacity, increased synthesis of pro-inflammatory cytokines and toxic mediators, and augmented complement-mediated phagocytosis. Thus, macrophages acquire the capacity for killing of bacteria, especially intracellular pathogens, and perhaps tumors[6]. Recent Reports suggest that monocyte derived macrophage have the capacity to lyse leukemic cells[7]. It was also reported that, treatment of chronic granulomatous disease (CGD) mice with IFN- also enhanced uptake of apoptotic cells by macrophage in vivo via the signalling pathway. "
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    ABSTRACT: Objectives: Murine macrophages were playing a key role against microbes and foreign particles as well as help in solid tumorigenesis in the host body. In this experiment we were trying to evaluate the protein tyrosine kinase (PTK) activity in macrophages from experimentally induced leukemic animal model. Methods: Balb/C mice were divided into four groups, two groups were challenged with N-N' ethyl nitrosourea (ENU) and two groups remained without ENU challenged condition. After confirmation of leukemia induction, one normal and one ENU challenged groups were received rmIL-3 and rmGM-CSF in combination for 4 consecutive days. Disease was confirmed by histological studies of peripheral blood and bone marrow smear. PTK activity assay were done using universal tyrosine kinase assay kit. Results: Protein tyrosine kinase (PTK) activity of macrophages was increased in leukemic animal significantly which were reduced after combination of IL-3 and GM-CSF treatment. IFN-γ level in blood serum was increased in leukemic mice and reinstates after treatment. Conclusion: Results suggest that, in leukemia reduced macrophage number can be increased by IL-3 and GM-CSF administration in combination but PTK activity is not involved to increase the number of macrophages. PTK activity may be involved in macrophage activation process in leukemic animal.
    06/2015; 6(606):385-390. DOI:10.7439/ijbr.v6i6.2186
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