PRODUCTION OF IL-5 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR BY NAIVE HUMAN MAST-CELLS ACTIVATED BY HIGH-AFFINITY IGE RECEPTOR LIGATION

Background: The late-phase allergic reaction is an eosinophilic inflam matory response that begins several hours after allergen exposure, may persist for 24 hours, and is an important pathogenic mechanism in all ergic disease. Objective: Cultured naive human mast cells were used to investigate whether mast cells are a direct source of the eosinophil- promoting cytokines IL-5, IL-3, and granulocyte-macrophage colony-stim ulating factor (GM-CSF). Methods: Naive human mast cells were derived from bone marrow mononuclear cells cultured in the presence of stem-ce ll factor. Cytokine message and protein production in response to high -affinity IgE receptor ligation of cultured mast cells were measured b y semiquantitative polymerase chain reaction and ELISA, respectively. Results: IL-5, IL-3, and GM-CSF messenger RNA increased within 2 hours of mast cell activation, with IL-5 and GM-CSF message remaining eleva ted for 24 hours, whereas IL-3 mRNA rapidly declined. IL-S and GM-CSF protein were measurable 4 to 6 hours after stimulation and peaked by 2 4 and 12 hours, respectively. IL-3 protein was not detectable. Conclus ion: These findings demonstrate that naive mast cells do not constitut ively produce IL-5 or GM-CSF protein but are a major source of these e osinophilotropic cytokines on high-affinity IgE receptor Ligation.