Expression and Production of the CXC Chemokine Growth-Related Oncogene-α by Human Eosinophils

Abstract

Eosinophils are seen together with neutrophils at sites of inflammation. However, their roles are not clear. In addition, eosinophils infiltrate tumor tissue in some neoplastic diseases. In this study, we show that large amounts of the neutrophil-activating CXC chemokine growth-related oncogene (GRO)-α can be produced by human eosinophils. Eosinophils showed presence of preformed GRO-α in the crystalloid-containing specific granules (190 pg/2 × 10⁶ cells). During incubation, a strong increase in GRO-α gene expression was seen. At a low cell density, addition of TNF-α or IL-1β increased the production of GRO-α in eosinophils, which was not the case at a higher cell density. Eosinophils can produce TNF-α themselves, and neutralizing Abs against TNF-α significantly inhibited GRO-α production. This suggests that autocrine and paracrine effects from TNF-α can be important when up-regulating GRO-α gene expression. In contrast, IFN-γ, a prototypic Th1-cytokine, down-regulated expression of GRO-α. This may be important during resolution of inflammation but also suggests different roles for eosinophils depending on the inflammatory context. Tumor-infiltrating eosinophils in Hodgkin’s disease of the nodular sclerosing type are associated with a poor prognosis. Eosinophils from such tumor tissue showed an abundant expression of GRO-α. The GRO-α receptor CXCR2 was also detected in tumor tissue, proposing interactions between eosinophils and the tumor. Our findings suggest that eosinophils can promote inflammation through recruitment of CXCR2-bearing cells. In addition, this feature of the eosinophils indicates a role for these cells in the biology of certain tumors.