Gene expression in mature neutrophils: early responses to inflammatory stimuli.
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.
Zhang
Xueqing
X
University of Massachusetts Medical School, LRB 404, 364 Plantation Street, Worcester, MA 01655, USA.
Kluger
Yuval
Y
Nakayama
Yasuhiro
Y
Poddar
Ranjana
R
Whitney
Constance
C
DeTora
Adam
A
Weissman
Sherman M
SM
Newburger
Peter E
PE
D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D016000:Cluster Analysis; D004926:Escherichia coli / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014157:Transcription Factors; D009240:N-Formylmethionine Leucyl-Phenylalanine