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Induction of intercellular adhesion molecule 1 (ICAM-1) expression in normal human eosinophils by inflammatory
W Czech1, J Krutmann, A Budnik
1Department of Dermatology, University of Freiburg, Germany.
Insights
Human eosinophils can be induced to express Intercellular Adhesion Molecule-1 (ICAM-1) by inflammatory cytokines like interferon gamma and tumor-necrosis factor alpha. This cytokine-induced ICAM-1 expression on eosinophils facilitates interactions with other inflammatory cells.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- Intercellular Adhesion Molecule-1 (ICAM-1) is vital for cell-cell interactions in inflammation, acting as a ligand for Lymphocyte Function-Associated Antigen-1 (LFA-1).
- Eosinophils are key effector cells in allergic skin diseases, and their interaction with LFA-1-positive leukocytes is crucial for inflammatory processes.
Purpose of the Study:
- To investigate the expression of ICAM-1 on human eosinophils.
- To determine the capacity of eosinophils to physically interact with LFA-1-positive inflammatory leukocytes.
Main Methods:
- Purified human eosinophils from peripheral blood were analyzed for ICAM-1 expression using fluorescence-activated cell sorter (FACS) analysis.
- Eosinophils were stimulated with various cytokines, including interferon gamma (IFN-γ), tumor-necrosis factor alpha (TNF-α), and interleukin-3 (IL-3), to assess ICAM-1 upregulation.
- Northern blot analysis was employed to confirm cytokine-induced ICAM-1 messenger RNA (mRNA) expression.
Main Results:
- Resting eosinophils from non-atopic individuals did not constitutively express ICAM-1.
- Stimulation with IFN-γ, TNF-α, or IL-3 significantly upregulated ICAM-1 surface expression in a time- and dose-dependent manner.
- Synergistic upregulation of ICAM-1 was observed with combinations of TNF-α and IFN-γ, IL-3, IL-5, or granulocyte/macrophage colony-stimulating factor (GM-CSF); IL-5 and GM-CSF alone did not induce expression.
- Specific cytokines like IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, C5a, and platelet-activating factor did not significantly affect eosinophil ICAM-1 expression.
Conclusions:
- Human eosinophils can be induced to express ICAM-1 upon stimulation with specific inflammatory cytokines.
- This cytokine-induced ICAM-1 expression enables adhesion-mediated interactions between eosinophils and LFA-1-positive cells.
- The study demonstrates a novel role for IL-3, IL-5, and GM-CSF in regulating ICAM-1 expression in human cells.
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.