title: Regulation of low affinity IgE receptor (CD23) expression on mononuclear phagocytes in normal and asthmatic subjects.
abstract: Mononuclear phagocytic cells contain low affinity receptors for IgE (Fc epsilon RII or CD23) which induce cellular activation in the presence of specific allergen. These studies were performed to quantify the expression by monocytes and alveolar macrophages of Fc epsilon RII in asthma and to determine biologic response modifiers that regulate Fc epsilon RII. Whereas 2.5 +/- 1.0% of the monocytes obtained from normal volunteers were Fc epsilon RII positive, this increased to 16.7 +/- 2.4% in asthma (p < 0.001). Stimulation of Fc epsilon RII expression on monocytes was shown to be an activity of IL-4 (24.5 +/- 5.9%), granulocyte-macrophage-CSF (28.1 +/- 5.2%), IFN-alpha (15.8 +/- 5.3%), IFN-gamma (10.4 +/- 3.7%), and macrophage-CSF (7.3 +/- 0.7%) but not of IL-2, IL-6, or TNF-alpha. Expression of Fc epsilon RII by these cytokines was associated with the induction of specific mRNA transcripts. Using Fc epsilon RII subtype specific primers in the polymerase chain reaction expansion of cDNA, cytokine-induced receptors were shown to be Fc epsilon RIIb. Alveolar macrophages from nonasthmatic subjects displayed minimal expression of Fc epsilon RII (3.2 +/- 1.2%); however, these receptors were present on 69.2 +/- 6.3% of asthmatic volunteers (p < 0.001). Induction of Fc epsilon RII appears specific for allergic asthma insofar as these receptors are also not expressed in subjects with interstitial lung disease (1.3 +/- 1.3%). As assessed by shift in mean fluorescence, instillation of allergen in the asthmatic's airway further up-regulated Fc epsilon RII on alveolar macrophages by 151 +/- 7%. Up-regulation of Fc epsilon RII in atopic individuals may therefore reflect allergen-induced exposure of mononuclear phagocytes to one or more of these cytokines. These studies suggest a mechanism by which an immunologic stimulus that leads to the production of these cytokines (e.g., allergen or viral infection) would contribute to the development or exacerbation of allergic disease.
authors.affiliation: Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: J J
authors.initials: JJ
authors.lastname: Mascali
authors.forename: H
authors.initials: H
authors.lastname: Smith
authors.forename: L J
authors.initials: LJ
authors.lastname: Rosenwasser
authors.forename: L
authors.initials: L
authors.lastname: Borish
mesh_terms: D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001483:Base Sequence; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000032:analysis* / Q000235:genetics
chemical_list: D000485:Allergens; D016207:Cytokines; D012333:RNA, Messenger; D017455:Receptors, IgE