Interleukin-3 is a differentiation factor for human basophils

Abstract

The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF-alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8-). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.