Induction of intercellular adhesion molecule 1 (ICAM-1) expression in normal human eosinophils by inflammatory cytokines.
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.
Czech
W
W
Department of Dermatology, University of Freiburg, Germany.
Krutmann
J
J
Budnik
A
A
Schöpf
E
E
Kapp
A
A
D015703:Antigens, CD; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology*; D004804:Eosinophils / Q000737:chemistry*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; C065289:ICAM2 protein, human; D007377:Interleukin-3; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma