1,721,237 research outputs found
Orchestration of macrophage polarization
No full textIn this issue of Blood, Ishii and colleagues shed new, fresh light on molecular mechanisms underlying one form of macrophage activation
Macrophages Have a Grip on the Gut
No full textWe host a world inside, and every day, new evidence reveals how relevant our microbiota is for daily living. In the most recent issue of Cell, Muller and colleagues demonstrate that microbiota commensals also influence colon peristalsis via a direct effect of muscolaris externae macrophages (Muller et al., 2014)
Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization lessons and open questions
No full textMacrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases
Systemic and cellular consequences of macrophage control of iron metabolism
No full textIron is necessary for both mammalian cells and microorganisms, which fiercely compete for this essential nutrient. Accordingly, macrophages exploit the denial of iron from microbial pathogens as an important strategy to accomplish their key role in innate immunity and host defense. Macrophages employ multiple mechanisms to accumulate iron and thus contain microbial infections, but this may come at a price. In particular, at the systemic level iron sequestration in the reticuloendothelial cells can lead to the development of anemia of chronic disease. At the local level, iron sequestration in macrophages, which is targeted to extracellular invaders, can in turn favor intracellular pathogens. Moreover, iron accumulation can per se promote pro-inflammatory activation of macrophages and consequently contribute to maintain the process of inflammation, without resolution. Finally, the peculiar iron trafficking that characterizes alternatively polarized macrophages can influence neighboring cells in the microenvironment and impact on the resolution phase of inflammation. In this review, we describe the role of macrophages in iron metabolism in the context of host defense and iron balance
New vistas on macrophage differentiation and activation
No full textPlasticity and heterogeneity are hallmarks of myelomonocytic differentiation and polarized activation. Evidence published in this issue of the European Journal of Immunology, together with other recent data, add new elements and perspectives to the current understanding of mononuclear phagocyte differentiation and activation and are discussed in this Commentary
Overview and potential unifying themes of the atypical chemokine receptor family
No full textChemokines modulate immune responses through their ability to orchestrate the migration of target cells. Chemokines directly induce cell migration through a distinct set of 7 transmembrane domain G protein-coupled receptors but are also recognized by a small subfamily of atypical chemokine receptors, characterized by their inability to support chemotactic activity. Atypical chemokine receptors are now emerging as crucial regulatory components of chemokine networks in a wide range of physiologic and pathologic contexts. Although a new nomenclature has been approved recently to reflect their functional distinction from their conventional counterparts, a systematic view of this subfamily is still missing. This review discusses their biochemical and immunologic properties to identify potential unifying themes in this emerging family
Hepatocyte growth factor enhances CXCR4 expression favoring breast cancer cell invasiveness
No full textMicroenvironmental factors affect different aspects of tumor cell biology, including cell survival, invasion, and metastasis. Here, we report that hepatocyte growth factor and hypoxia may contribute to breast carcinoma cell invasiveness by inducing the chemokine receptor CXCR4. Hepatocyte growth factor enhanced CXCR4 mRNA and protein expression exclusively in MCF-7 (low invasive) carcinoma cells, while in response to hypoxia, CXCR4 induction was observed in both MCF-7 and MDA-MB 231 (highly invasive) carcinoma cells. The receptor induction had a functional role in cancer cells, as demonstrated by the fact that hepatocyte growth factor pretreatment promoted MCF-7 cell migration toward the CXCR4-specific ligand CXCL12. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) and phosphoinositide-3-kinase (PI3K) transduction pathways seemed to be differently implicated in the early induction of CXCR4 by hepatocyte growth factor or hypoxia in the two breast carcinoma cells examined
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