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.