Effect of FcγR on FcεR -Mediated Reactions in Human Basophils

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Human basophils are implicated through FcεRI-mediated reactions in allergic diseases such as bronchial asthma. However, the role of FcγR on basophils remains uncertain. The purpose of this study is to clarify the effect of FcγR on FcεRI-mediated reactions in human basophils. We obtained basophils by culturing G-CSF mobilized peripheral blood stem cell (PBSC)-rich mononuclear cells from patients with malignant lymphoma and lung cancer. PBSC-rich mononuclear cells were cultured in the presence of rhIL-3. After 3 weeks of culture, 35-80% of the cells were identified as basophils by light and electron microscopy and histamine assay. Flow cytometric analysis has shown that they express FcγRII as well as FcεRI.Stimulation of FcεRI and FcγRII, either separately or simultaneously, resulted in a rapid calcium influx. Stimulation of FcεRI evoked histamine release. Coligation of FcγRII to FcεRI could not inhibit the calcium response or histamine release following FcεRI crosslinking. Crosslinking of FcγRII on cells expressing both FcγRIIa and FcγRIIb will result in a signal whose intensity is dependent on the balance between both positive and negative signaling. The result that crosslinking of FcγRII on basophils induced a rapid calcium influx without inhibition of IgE-mediated calcium influx or histamine release indicates the predominance of FcγRIIa in FcγRII signaling. Our findings suggest that FcγRII on human basophils may not inhibit FcεRI-mediated signaling because of the positive signal by FcγRIIa.