Induction of Intercellular Adhesion Molecule 1 (ICAM-1) Expression in Normal Human Eosinophils by Inflammatory Cytokines

Abstract

Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand for lymphocyte function-associated antigen-1 (LFA-1), and thereby plays a crucial role in mediating cell-cell interactions in inflammatory reactions. Human eosinophils represent important effector cells in allergic skin diseases. To gain more insight into the capacity of eosinophils to physically interact with LFA-1-positive inflammatory leukocytes, in the present study ICAM-1 expression in eosinophils was investigated. Using fluorescence-activated cell sorter analysis, it could be shown that highly purified (> or = 95%) eosinophils from peripheral blood of non-atopic individuals do not constitutively express ICAM-1 molecules. However, stimulation of eosinophils with interferon gamma (IFN gamma), tumor-necrosis factor alpha (TNF alpha), or interleukin 3 (IL-3) markedly upregulated ICAM-1 surface expression in a time- and dose-dependent manner. Cytokine-induced ICAM-1 expression in human eosinophils was corroborated by Northern blot analysis. Accordingly, unstimulated eosinophils did not express significant amounts of ICAM-1 mRNA, but ICAM-1 mRNA expression could be markedly induced in these cells upon stimulation with IFN gamma plus TNF alpha. The combination of TNF alpha with either IFN gamma, IL-3, IL-5, or granulocyte/macrophage colony-stimulating factor (GM-CSF) increased ICAM-1 expression in a synergistic fashion, whereas IL-5 or GM-CSF by itself did not induce ICAM-1 expression. Cytokine-induced ICAM-1 expression was specific, because IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-7, IL-8, C5a, and platelet-activating factor did not significantly affect eosinophil ICAM-1 surface expression. In summary, these studies indicate that eosinophils may be activated to express the adhesion molecule ICAM-1 upon stimulation with selected inflammatory cytokines, which may allow adhesion-mediated cross-talk between eosinophils and LFA-1-positive cells. In addition, these data demonstrate for the first time a role for IL-3, IL-5, and GM-CSF in regulation of ICAM-1 expression in human cells.