title: Gene expression in human neutrophils during activation and priming by bacterial lipopolysaccharide.
abstract: Circulating neutrophils play a key role both in the systemic inflammatory response and in complications of bacterial infection such as septic shock and septic multiple organ dysfunction syndrome. We have analyzed gene expression patterns in human neutrophils stimulated by E. coli lipopolysaccharide (LPS), with or without prior exposure to LPS, using differential display and oligonucleotide chip techniques. We identified 307 genes that were activated or repressed after treatment with LPS at 10 ng/ml and 385 genes after LPS at 100 ng/ml, compared with untreated neutrophils. The two sets included many transcription factors, cytokines, chemokines, interleukins, and surface antigens, as well as members of the toll-like receptor, Rel/NF-kappaB, and immune mediator gene families. Time course analysis showed that the early and late neutrophil responses to LPS share some common mechanisms, but many changes in gene expression are transient or late to develop. Neutrophils also showed a priming response to LPS, in which 97 genes significantly changed expression on re-exposure to lower dose LPS and were analyzed by unsupervised hierarchical clustering. These findings indicate that the neutrophil is a transcriptionally active cell responsive to environmental stimuli and capable of a complex series of both early and late changes in gene expression. Supplementary material for this article can be found on the Journal of Cellular Biochemistry website (http://jws-edci.interscience.wiley.com:8998/jpages/0730-2312/suppmat/89/v89.page.html).
authors.affiliation: Department of Genetics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsukahara
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lian
authors.forename: Xueqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Constance
authors.initials: C
authors.lastname: Whitney
authors.forename: Yuval
authors.initials: Y
authors.lastname: Kluger
authors.forename: David
authors.initials: D
authors.lastname: Tuck
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Sherman M
authors.initials: SM
authors.lastname: Weissman
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
mesh_terms: D016000:Cluster Analysis; D004926:Escherichia coli / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D005810:Multigene Family; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000032:analysis / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D012313:RNA