Granulocyte-macrophage colony-stimulating factor stimulates macrophages to respond to IgE via the low affinity IgE receptor (CD23).
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 (Fc epsilon RII or CD23) are not expressed on monocytes obtained from healthy, nonatopic donors. Fc epsilon RII 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% Fc epsilon RII-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).(ABSTRACT TRUNCATED AT 250 WORDS)
Matz
J
J
National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Sciences Center, Denver 80206.
Williams
J
J
Rosenwasser
L J
LJ
Borish
L C
LC
D001249:Asthma / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D017455:Receptors, IgE / Q000502:physiology*; D012016:Reference Values
D016207:Cytokines; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor