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Originally published online as doi:10.1189/jlb.0903412 on November 21, 2003

Published online before print November 21, 2003
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(Journal of Leukocyte Biology. 2004;75:358-372.)
© 2004 by Society for Leukocyte Biology

Gene expression in mature neutrophils: early responses to inflammatory stimuli

Xueqing Zhang*, Yuval Kluger{dagger}, Yasuhiro Nakayama{dagger}, Ranjana Poddar{dagger}, Constance Whitney*, Adam DeTora*, Sherman M. Weissman{dagger} and Peter E. Newburger*,1

* Department of Pediatrics and Cancer Center, University of Massachusetts School of Medicine, Worcester; and the
{dagger} Department of Genetics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut

1 Correspondence: Department of Pediatrics and Cancer Center, University of Massachusetts Medical School, LRB 404, 364 Plantation Street, Worcester, MA 01655. E-mail: peter.newburger{at}umassmed.edu

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.

Key Words: mRNA • transcription • transcription factor • chromatin




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