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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1379. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Friedman, A. D. Search for Related Content PubMed Articles by Friedman, A. D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Comment on Theilgaard-Mönch et al, page 1785 A microarray window into granulocyte development and function Alan D. Friedman JOHNS HOPKINS UNIVERSITY This study provides a detailed analysis of gene expression patterns during granulocytic maturation and in so doing provides novel insights into myeloid cell development and activities. As part of the innate immune system, granulocytes are essential for host defense against invading microorganisms. Theilgaard-Mönch and colleagues have applied microarray analysis to uncover the weapons these short-lived cells bring to this task and the complex program that allows neutrophils to develop from immature myeloblasts. Density gradient centrifugation followed by immunodepletion of other lineages allowed purification of myeloblast/promyelocyte (PM), myelocyte/metamyelocyte (MY), and band cell/polymorphonuclear leukocyte (bm-PMN) populations from human marrow and of a pb-PMN population from human peripheral blood. A variety of RNAs encoding regulatory receptors were identified in PMNs, including interferon, interleukin, chemokine, and tumor necrosis factor receptors and members of the leukocyte immunoglobulin (Ig)–like receptor family also present in monocytes. Receptors that recognize microorganisms directly or through antibody intermediates were also up-regulated as were cytokines and chemokines that may allow autocrine control. In addition, novel secondary granule proteins, such as galectin-3 and its receptors, haptoglobin, and several protease inhibitors were uncovered. These new insights into expression of proteins that control and effect granulocyte functions in defense against a spectrum of microorganisms will enable future studies to understand and even improve innate immunity. Granulocyte lineage cell populations used for microarray analysis. See the complete figure in the article beginning on page 1785.   Granulocytes are born to die, perhaps as a means of protecting the host against their toxic contents. While p53 was down-regulated in granulocytes, histone H1.2, an inducer of apoptosis, increased as did death receptors and their ligands and several proapoptotic BH3-only proteins. The roles of each of these molecules in neutrophil survival also bear further investigation. The microarray data obtained should also assist investigations focused on the transcriptional program mediating the development of granulocytes from myeloblasts. While the roles of CCAAT/enhancer-binding protein- (C/EBP), C/EBP, PU.1, retinoic acid receptor (RAR), CCAAT displacement protein (CDP), and several other factors have been described,1 additional transcription factors, coactivators, corepressors, and histone-modifying and remodeling proteins are likely involved. Cell-cycle inhibition mediated by interaction of C/EBPs with E2 promoter binding factor (E2F) may also facilitate terminal maturation,2,3 and indeed the array data demonstrate down-regulation of multiple E2F genetic targets during the promyelocyte to myelocyte transition. References Friedman AD. Transcriptional regulation of granulocyte and monocyte development. Oncogene. 2002;21: 3377-3390.[CrossRef][Medline] [Order article via Infotrieve] Porse BT, Pederson TA, Xu X, et al. E2F repression by C/EBP is required for adipogenesis and granulopoiesis in vivo. Cell. 2001;107: 247-258.[CrossRef][Medline] [Order article via Infotrieve] Wang QF, Friedman AD. CCAAT/enhancer binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor. Blood. 2002;99: 2776-2785.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The transcriptional program of terminal granulocytic differentiation Kim Theilgaard-Mönch, Lars Christian Jacobsen, Rehannah Borup, Thomas Rasmussen, Malene Digmann Bjerregaard, Finn Cilius Nielsen, Jack Bernard Cowland, and Niels Borregaard Blood 2005 105: 1785-1796. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Friedman, A. D. Search for Related Content PubMed Articles by Friedman, A. D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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