Granulocyte-macrophage colony-stimulating factor stimulates macrophages to respond to IgE via the low affinity IgE receptor (CD23)

Abstract

We have found increased concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid of 11 patients with nocturnal asthma (15.3 ± 4.6 pg/ml) compared with normal subjects (2.3 ± 6.1 pg/ml) ( p = 0.03). In contrast to patients with asthma, low affinity IgE receptors (FcϵRII or CD23) are not expressed on monocytes obtained from healthy, nonatopic donors. FcϵRII expression was induced by the cytokines GM-CSF and interleukin (IL)-4 either alone or in combination. As assessed by flow cytometry, the combination of IL-4 and GM-CSF was found to be synergistic, inducing up to 54.8% ± 4.6% FcϵRII-positive monocytes compared with a maximum of 27.4% ± 5.0% and 30.0% ± 4.0% with IL-4 and GM-CSF alone, respectively ( p < 0.05 compared with either cytokine alone). Human monocytes from the peripheral blood of seven normal subjects were cultured for 24 hours with and without IL-4 or GM-CSF. With IL-4, addition of IgE/anti-IgE complexes failed to induce IL-1 secretion and inhibited IL-1 secretion induced by lipopolysaccharides. The addition of GM-CSF or IgE immune complexes alone resulted in no additional IL-1 secretion in supernatants of the untreated monocytes, whereas the IgE complexes did stimulate IL-1 secretion by monocytes cultured in GM-CSF, as measured by ELISA (from 0.7 ± 0.2 ng/ml to 2.3 ± 0.5 ng/ml; p < 0.01). This could be confirmed to represent an FcϵRII-dependent process insofar as blocking of the FcϵRII receptors abrogated the capacity of the IgE complexes to induce IL-1β (1.0 ± 0.4 ng/ml IL-1; p = NS in comparison with untreated monocytes). We conclude that GM-CSF is increased in the bronchoalveolar lavage fluid of patients with asthma and may be important in macrophage activation via induction of the low affinity IgE receptor, thereby making cells susceptible to IgE-dependent activation. (J A LLERGY C LIN I MMUNOL 1994;93:650-7.)