Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes

Am J Respir Cell Mol Biol. 2001 Oct;25(4):425-33. doi: 10.1165/ajrcmb.25.4.4456.

Abstract

The increase in eosinophils at the site of antigen challenge has been used as evidence to suggest that this cell type plays a role in the pathophysiology of asthma. Aberrant production of several different cytokines, particularly interleukin (IL)-5, has been shown to result in eosinophilia. IL-5 influences the development and maturation of eosinophils in a number of different ways. Of note is the ability of IL-5 to act as a survival factor for eosinophils specifically inhibiting apoptosis. The precise mechanism by which IL-5 exerts its effect remains obscure. We used microarray technologies to investigate the changes in the messenger RNA expression profile of eosinophils after treatment with IL-5. Using the Affymetrix Hu6800 chip, a total of 80 genes were observed to be regulated by 2-fold or greater. Many of the genes previously identified as regulated by IL-5 were regulated in our microarray experiments. Of the 73 genes found to be upregulated, many were shown to play a role in adhesion, migration, activation, or survival of eosinophils or hematopoietic cells, whereas the function of others was unknown. To facilitate the identification of genes that govern the apoptosis and survivability of eosinophils, we used an alternative cellular model, TF1.8 cells, whose survival was also dependent on IL-5. Comparison of these models identified four genes, Pim-1, DSP-5 (hVH3, B23), CD24, and SLP-76, whose regulation was similarly coordinated in both systems. Identification of Pim-1 and SLP-76 as regulated by IL-5 led us to suggest a direct role for these proteins in the IL-5 signaling pathway in eosinophils. The tissue distribution of these genes demonstrated that Pim-1 and SLP-76 were relatively restricted to the eosinophil compared with their expression in brain, bone marrow, kidney, liver, and lung. By contrast, DSP-5 and CD24 were confirmed as ubiquitous in their expression by microarray.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Apoptosis / genetics*
  • CD24 Antigen
  • Cell Survival / genetics
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • Dual-Specificity Phosphatases
  • Early Growth Response Protein 1
  • Eosinophils / cytology*
  • Eosinophils / physiology*
  • Humans
  • Immediate-Early Proteins*
  • Interleukin-5 / metabolism*
  • Interleukin-5 / pharmacology
  • Lectins, C-Type
  • Membrane Glycoproteins*
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis*
  • Phosphoproteins / genetics
  • Protein Tyrosine Phosphatases / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-pim-1
  • Transcription Factors / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD24 Antigen
  • CD24 protein, human
  • CD69 antigen
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • Interleukin-5
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • SLP-76 signal Transducing adaptor proteins
  • Transcription Factors
  • PIM1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1
  • DUSP5 protein, human
  • Dual-Specificity Phosphatases
  • Protein Tyrosine Phosphatases

Associated data

  • GENBANK/U15932