Microarray analysis of lipopolysaccharide-treated human neutrophils.
Neutrophils respond to infection by degranulation, release of reactive oxygen intermediates, and secretion of chemokines and cytokines; however, activation of neutrophil transcriptional machinery has been little appreciated. Recent findings suggest that gene expression may represent an additional neutrophil function after exposure to lipopolysaccharide (LPS). We performed microarray gene expression analysis of 4,608 mostly nonredundant genes on LPS-stimulated human neutrophils. Analysis of three donors indicated some variability but also a high degree of reproducibility in gene expression. Twenty-eight verifiable, distinct genes were induced by 4 h of LPS treatment, and 13 genes were repressed. Genes other than cytokines and chemokines are regulated; interestingly, genes involved in cell growth regulation and survival, transcriptional regulation, and interferon response are among those induced, whereas genes involved in cytoskeletal regulation are predominantly repressed. In addition, we identified monocyte chemoattractant protein-1 as a novel LPS-regulated chemokine in neutrophils. Included in these lists are five clones with no defined function. These data suggest molecular mechanisms by which neutrophils respond to infection and indicate that the transcriptional potential of neutrophils is greater than previously thought.
Malcolm
Kenneth C
KC
Department of Medicine, National Jewish Medical and Research Center, Denver 80206, USA. malcolmk@njc.org
Arndt
Patrick G
PG
Manos
Elizabeth J
EJ
Jones
David A
DA
Worthen
G Scott
GS
D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards; D015203:Reproducibility of Results; D015854:Up-Regulation / Q000235:genetics
D008070:Lipopolysaccharides