Generation of Diversity in the Innate Immune System: Macrophage Heterogeneity Arises from Gene-Autonomous Transcriptional Probability of Individual Inducible Genes

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...

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Published inThe Journal of immunology (1950) Vol. 168; no. 1; pp. 44 - 50
Main Authors Ravasi, Timothy, Wells, Christine, Forest, Alistair, Underhill, David M, Wainwright, Brandon J, Aderem, Alan, Grimmond, Sean, Hume, David A
Format Journal Article
LanguageEnglish
Published United States Am Assoc Immnol 01.01.2002
Subjects
Animals
Cell Line
Clone Cells
DNA microarrays
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - genetics
Gene Expression Profiling
Genes, Reporter
Genetic Variation
Kruppel-Like Transcription Factors
Lipopolysaccharides - pharmacology
Luciferases - genetics
Luciferases - metabolism
Macrophage Activation
Macrophages - drug effects
Macrophages - immunology
Mice
Nerve Tissue Proteins
Oligonucleotide Array Sequence Analysis
Repressor Proteins
RNA, Messenger - biosynthesis
Transcription Factors - biosynthesis
Transcription Factors - genetics
Transcriptional Activation
Transfection
Xenopus Proteins
Zinc Finger Protein Gli3
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Summary: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-alpha 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.
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ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.1.44