Human recombinant histamine-releasing factor activates human eosinophils and the eosinophilic cell line, AML14-3D10

The human recombinant histamine-releasing factor (HrHRF) was previously sho wn to induce histamine release from human basophils from a subset of donors , The ability of HrHRF to directly induce histamine release from only certa in basophils was thought to involve interaction between HrHRF and a particu lar kind of IgE, termed IgE(+), on the surface of these cells. Recent studi es disproved the hypothesis that the IgE molecule or its high-affinity rece ptor, Fc epsilon RI, is involved in secretion of histamine and cytokines by basophils stimulated with HrHRF. Rather, data suggest that HrHRF is a cyto kine that stimulates basophils by binding to a cell-surface structure other than the IgE molecule. This report describes the effects of HrHRF on anoth er inflammatory cell type: eosinophils from mildly allergic donors. In puri fied eosinophils primed with granulocyte-macrophage colony-stimulating fact or, both tumor necrosis factor alpha (TNF-alpha) and HrHRF induced increase d secretion of interleukin (IL) 8. In addition, both HrHRF and IL-5 enhance d secretion of IL-8 stimulated by TNF-alpha. Secretion of IL-8 reached a pl ateau level in less than 24 hours, was inhibited by cycloheximide, and requ ired the presence of HrHRF throughout the culture period. In some eosinophi l preparations, HrHRF induced calcium mobilization that was inhibited by pe rtussis toxin. Additionally, HrHRF caused secretion of IL-8 from the human eosinophilic cell line, AML-14-3D10, which does not possess the cu chain of Fc epsilon RI. These data provide evidence that HrHRF contributes to activ ation of eosinophils and thus suggest an additional role for HrHRF in the p athophysiologic mechanisms of allergic disease. (Blood. 2000;96:2191-2198) (C) 2000 by The American Society of Hematology.