Generation of diversity in the innate immune system: Macrophage heterogeneity arises from gene-autonomous transcriptional probability of individual inducible genes

T. Ravasi, C. Wells, A. Forrest, D. M. Underhill, B. J. Wainwright, A. Aderem, S. Grimmond, D. A. Hume*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Microbial products such as LPS stimulate macrophages to produce a wide diversity of inducible gene products needed for immediate host defense and priming of an appropriate acquired immune response. In this study, we have examined LPS-inducible gene expression in subclones of a mouse macrophage cell line, RAW264, using cDNA microarrays. Even archetypal target genes such as TNF-α were not induced in all subclones, and there was no absolute correlation between expression of pairs of genes. Nevertheless, the array analysis revealed clusters of genes that were more likely to be coexpressed. RAW264 cells stably transfected with luciferase reporter genes driven by LPS-responsive promoters revealed the same kind of clonal heterogeneity. The results indicate that each LPS-inducible gene has its own inherent probability of activation in response to LPS.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalJournal of Immunology
Volume168
Issue number1
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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