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

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 pathophysiol ogy of asthma. Aberrant production of several different cytokines, particul arly interleukin (IL)-5, has been shown to result in eosinophilia. IL-5 inf luences the development and maturation of eosinophils in a number of differ ent ways. Of note is the ability of IL-5 to act as a survival factor for eo sinophils 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 eosinop hils after treatment with IL-5. Using the Affymetrix Hu6800 chip, a total o f 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 micr oarray experiments. Of the 73 genes found to be upregulated, many were show n to play a role in adhesion, migration, activation, or survival of eosinop hils or hematopoietic cells, whereas the function of others was unknown. To facilitate the identification of genes that govern the apoptosis and survi vability of eosinophils, we used an alternative cellular model, TF1.8 cells , whose survival was also dependent on IL-5. Comparison of these models ide ntified four genes, Pim-1, DSP-5 (hVH3, B23), CD24, and SLP-76, whose regul ation was similarly coordinated in both systems. identification of Pim-1 an d SLP-76 as regulated by IL-5 led us to suggest a direct role for these pro teins in the IL-5 signaling pathway in eosinophils. The tissue distribution of these genes demonstrated that Pim-1 and SLP-76 were relatively restrict ed to the eosinophil compared with their expression in rain bone marrow, ki dney, liver, and lung. By contrast, DSP-5 and CD24 were confirmed as ubiqui tous in their expression by microarray.