Article

Identification of a common gene signature for type II cytokine-associated myeloid cells elicited in vivo in different pathologic conditions.

Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Belgium.
Blood (Impact Factor: 9.78). 08/2006; 108(2):575-83. DOI: 10.1182/blood-2005-04-1485
Source: PubMed

ABSTRACT Compared with type I cytokine-associated myeloid (M1) cells, the molecular repertoire and mechanisms underlying functional properties of type II cytokine-associated myeloid (M2) cells are poorly characterized. Moreover, most studies have been limited to in vitro-elicited M2 cells. Here, comparative gene expression profiling of M1 and M2 cells, elicited in murine models of parasitic infections and cancer, yielded a common signature for in vivo-induced M2 populations independent of disease model, mouse strain, and organ source of cells. Some of these genes, such as cadherin-1, selenoprotein P, platelet-activating factor acetylhydrolase, and prosaposin, had not been documented as associated with M2. Overall, the common signature genes provide a molecular basis for a number of documented or suggested properties of M2, including immunomodulation, down-regulation of inflammation, protection against oxidative damage, high capacity for phagocytosis, and tissue repair. Interestingly, several common M2 signature genes encode membrane-associated markers that could be useful for the identification and isolation of M2. Some of these genes were not induced by IL-4/IL-13 or IL-10 under various in vitro settings and thus were missed in approaches based on in vitro-activated cells, validating our choice of in vivo models for expression profiling of myeloid cells.

0 Bookmarks
 · 
87 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The current review article describes the functional relationship between tumor-associated macrophages (TAM) as key cellular contributors to cancer malignancy on the one hand and macrophage-colony-stimulating factor (M-CSF or CSF-1) as an important molecular contributor on the other. We recapitulate the available data on expression of M-CSF and the M-CSF receptor (M-CSFR) in human tumor tissue as constituents of a stromal macrophage signature and on the limits of the predictive and prognostic value of plasma M-CSF levels. After providing an update on current insights into the nature of TAM heterogeneity at the level of M1/M2 phenotype and TAM subsets, we give an overview of experimental evidence, based on genetic, antibody-mediated, and pharmacological disruption of M-CSF/M-CSFR signaling, for the extent to which M-CSFR signaling can not only determine the TAM quantity, but can also contribute to shaping the phenotype and heterogeneity of TAM and other related tumor-infiltrating myeloid cells (TIM). Finally, we review the accumulating information on the - sometimes conflicting - effects blocking M-CSFR signaling may have on various aspects of cancer progression such as tumor growth, invasion, angiogenesis, metastasis, and resistance to therapy and we thereby discuss in how far these different effects actually reflect a contribution of TAM.
    Frontiers in Immunology 10/2014; 5:489. DOI:10.3389/fimmu.2014.00489
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Perinatal depression is an emerging field with questions that remain to be answered, including the underlying pathogenesis, treatment and counseling. Pregnant women with depression represent a serious risk to themselves due to negative fetal/obstetrical and neonatal outcomes and to their child with respect to development later in life. The immune system plays a crucial role in major depression disorder (MDD), and studies indicate that both immune mediators (cytokines, chemokines) and neuroendocrine hormones cross-talk in MDD. However, the innate immune system is an unexplored field, and its link with prenatal depression has not been fully explored. The innate immune system is tightly regulated during early implantation and placentation of the conceptus, and such regulation is crucial for a successful pregnancy. T lymphocytes, which comprise helper T lymphocytes (Th), and cytotoxic T lymphocytes (CTLs), have been shown to be abundant at the fetomaternal interface together with the recruitment of different subsets of immune cells [Natural Killer cells (NK), Dendritic cells (DCs), Macrophages (Mφs)] during decidualization of the endometrium. Pregnancy is considered to be an inflammatory process in which a Th2 over a Th1 immune response is critical for allowing the development of the fetal allograft. Stressful stimuli and prenatal infections have been shown to deregulate the Th1/Th2 balance and are associated with increased production of proinflammatory cytokines and modification of neonatal immune responses via toll-like receptor (TLR) signaling. The innate immune system could represent a new frontier in exploring the etiology of several mental disorders, as suggested for schizophrenia. However, it is not clear how the innate immune system cross-talks with the fetal brain during perinatal depression.
    Current Psychiatry Reviews 08/2014; 10(3). DOI:10.2174/1573400509666131217010344
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Starting point for the present work was the assumption that the cell line MuMac-E8 represents a murine cell population with stem cell properties. Preliminary studies already pointed to the expression of stem-cell associated markers and a self-regenerative potential of the cells. The cell line MuMac-E8 should be examined for their differential stage within stem cell hierarchy. MuMac-E8 cells were derived from a chimeric mouse model of arthritis. It could be shown that MuMac-E8 cells express mRNA of some genes associated with pluripotent stem cells (Nanog, Nucleostemin), of genes for hematopoietic markers (EPCR, Sca-1, CD11b, CD45), for the mesenchymal marker CD105 and of genes for the neural markers Pax-6 and Ezrin. In methylcellulose and May-Grünwald-Giemsa staining, hematopoietic colonies were obtained but the hematopoietic system of lethally irradiated mice could not be rescued. Osteogenic differentiation was not detectable. Thus, it became evident that MuMac-E8 represents not a stem cell line. However, MuMac-E8 cells expressed several myeloid surface markers (i.e. CD11b, F4/80, CD14, CD64), showed phagocytosis and is capable of producing nitric oxide. Thus, this cell line seems to be arrested an advanced stage of myeloid differentiation. Adherence data measured by impedance-based real-time cell analysis together with cell morphology data suggested that MuMac-E8 represents a new macrophage precursor cell line exhibiting weak adherence. This cell line is suitable as an in-vitro model for testing of macrophage functions. Moreover, it might be also useful for differentiation or reprogramming studies.
    PLoS ONE 12/2014; 9(12):e113743. DOI:10.1371/journal.pone.0113743 · 3.53 Impact Factor

Full-text (2 Sources)

Download
29 Downloads
Available from
May 30, 2014