Microarray analysis of lipopolysaccharide-treated human neutrophils

Kenneth C. Malcolm, Patrick G. Arndt, Elizabeth J. Manos, David A. Jones, G. Scott Worthen

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)L663-L670
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume284
Issue number4 28-4
DOIs
StatePublished - Apr 1 2003

Keywords

  • Cellular activation
  • Gene regulation
  • Host defense
  • Toll-like receptor

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