Project description:Uterine Mast cells (MCs) are essential for placentation, implantation and growth of fetus. In contrast, the functions of placental MCs are poorly investigated. The objective of the study was to evaluate the transcriptional profile of human placental MCs using whole genome microarray. We isolated MCs from placenta from healthy at term donors with CD117 and IgE antibodies, and used HMC-1.2 cell lines as controls. Data analysis revealed 16,468 genes modulated in human placenta MCs as compared with HMC-1.2 cell lines; most of them (83%) were up-regulated. The differentially expressed genes in placental MCs were enriched with three biological categories: immune response, FcReI signaling and reproduction processes. The two first categories revealed the importance of immune gene expression including chemokines, cytokines, interferon, and major histocompatibility complex antigens in placental MCs. A set of genes were modulated in FcReI process suggesting a role of IgE-mediated activation. Finally, in pregnancy category, we identified specific genes of WNT pathway and those involved in response to estrogen and progesterone. Taken together, human placental MCs exhibited a unique transcriptional profile enriched with immune response and pregnancy genes, which reflects the impact of placenta environment on MC functions.
Project description:Mast cells are hematopoietic cells that reside preferentially in tissues exposed to internal and external environments. Mast cells sense immunological, inflammatory and environmental stimuli, and can be activated to release granules and generate inflammatory mediators. Mast cell-derived products confer protection against snake venoms and some parasite infections. Aberrant activation of mast cells is a major contributor to human pathology, including allergy, asthma and adverse drug reactions. Their strict tissue location has largely impeded the isolation of large numbers of primary mast cell for further analysis. To better understand the biology of mast cells, we analyzed the proteome of primary human and mouse mast cells by quantitative mass spectrometry. We identified a mast cell-specific protein signature that was conserved from mouse to man. Compared to a comprehensive set of other immune cell lineages, proteome analysis identified a unique and distant mast cell cluster. The mast cell signature included proteins governing granule biosynthesis and secretion, as well as proteoglycan- and neurotransmitter metabolism. Proteome conservation across species suggests evolutionary maintenance of mast cell functions.
Project description:BACKGROUND: In asthma and other allergic disorders, the activation of mast cells by IgE and antigen induces the cells to release histamine and other mediators of inflammation, as well as to produce certain cytokines and chemokines. To search for new mast cell products, we used complementary DNA microarrays to analyze gene expression in human umbilical cord blood-derived mast cells stimulated via the high-affinity IgE receptor (FcϵRI). : One to two hours after FcϵRI-dependent stimulation, more than 2,400 genes (about half of which are of unknown function) exhibited 2-200 fold changes in expression. The transcriptional program included changes in the expression of IL-11 and at least 30 other cytokines and chemokines. Human mast cells secreted 130-529 pg of IL-11/106 cells by 6 h after stimulation with anti-IgE. CONCLUSION: Our initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the FcϵRI has identified many products that heretofore have not been associated with this cell type, but which may significantly influence mast cell function in IgE-associated host responses. We also have demonstrated that mast cells stimulated via the FcϵRI can secrete IL-11. Based on the previously reported biological effects of IL-11, our results suggest that production of IL-11 may represent one link between IgE-dependent mast cell activation in subjects with allergic asthma and the development of a spectrum of structural changes in the airways of these individuals; such changes, collectively termed "airway remodeling," can constitute an important long term consequence of asthma. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
Project description:Mast cells are known to be the key players in type I hypersensitivity reactions in humans and mice. They are critically involved in the development of allergic rhinitis, allergic asthma and systemic anaphylaxis. In this study we investigated the role of the transcriptional regulator MAZR in mast cells by comparing the expression profile of mast cells generated from wild-type (MazrF/F) and MAZR-deficient (MazrF/F x Vav-iCre) bone marrow cells. Our results from the array data demonstrate that MAZR acts preferentially as a transcriptional repressor in mast cells.
Project description:Mast cells are hematopoietic cells that reside preferentially in tissues exposed to internal and external environments. Mast cells sense immunological, inflammatory and environmental stimuli, and can be activated to release granules and generate inflammatory mediators. Mast cell-derived products confer protection against snake venoms and some parasite infections. Aberrant activation of mast cells is a major contributor to human pathology, including allergy, asthma and adverse drug reactions. Their strict tissue location has largely impeded the isolation of large numbers of primary mast cell for further analysis. To better understand the biology of mast cells, we analyzed the proteome of primary mouse mast cells by quantitative mass spectrometry