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    Gene expression in mature neutrophils: early responses to inflammatory stimuli

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    Authors
    Zhang, Xueqing
    Kluger, Yuval
    Nakayama, Yasuhiro
    Poddar, Ranjana
    Whitney, Constance
    DeTora, Adam
    Weissman, Sherman M.
    Newburger, Peter E.
    UMass Chan Affiliations
    Department of Pediatrics
    Document Type
    Journal Article
    Publication Date
    2004-02-01
    Keywords
    Chromatin Assembly and Disassembly
    Cluster Analysis
    Escherichia coli
    Gene Expression Profiling
    Gene Expression Regulation
    Humans
    Inflammation Mediators
    Lipopolysaccharides
    N-Formylmethionine Leucyl-Phenylalanine
    Neutrophils
    Time Factors
    Transcription Factors
    Hematology
    Oncology
    Pediatrics
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    Link to Full Text
    http://dx.doi.org/10.1189/jlb.0903412
    Abstract
    Neutrophils provide an essential defense against bacterial and fungal infection and play a major role in tissue damage during inflammation. Using oligonucleotide microarrays, we have examined the time course of changes in gene expression induced by stimulation with live, opsonized Escherichia coli, soluble lipopolysaccharide, and the chemoattractant formyl-methionyl-leucyl-phenylalanine. The results indicate that activated neutrophils generate a broad and vigorous set of alterations in gene expression. The responses included changes in the levels of transcripts encoding 148 transcription factors and chromatin-remodeling genes and 95 regulators of protein synthesis or stability. Clustering analysis showed distinct temporal patterns with many rapid changes in gene expression within the first hour of exposure. In addition to the temporal clustering of genes, we also observed rather different profiles associated with each stimulus, suggesting that even a nonvirulent organism such as E. coli is able to play a dynamic role in shaping the inflammatory response. Principal component analysis of transcription factor genes demonstrated clear separation of the neutrophil-response clusters from those of resting and stimulated human monocytes. The present study indicates that combinatorial transcriptional regulation including alterations of chromatin structure may play a role in the rapid changes in gene expression that occur in these terminally differentiated cells.
    Source
    J Leukoc Biol. 2004 Feb;75(2):358-72. Epub 2003 Nov 21. doi: 10.1189/jlb.0903412
    DOI
    10.1189/jlb.0903412
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/43385
    PubMed ID
    14634056
    Related Resources
    Link to article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1189/jlb.0903412
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