Stimulation of eosinophil IgE low-affinity receptor leads to increased adhesion molecule expression and cell migration.

Immunoglobulin binding on eosinophil surface receptors results in activation of these cells. Evaluating blood eosinophils from atopic subjects, it was investigated whether ligation of immunoglobulin E low-affinity receptor (FcepsilonRII/ CD23) with specific monoclonal antibodies (Mabs) resulted in enhanced eosinophil migration and adhesion molecule expression. Eosinophils from 20 subjects with allergic asthma (atopic individuals) and nine nonatopic normal individuals (controls) were purified using Percoll gradients. The effect of antihuman CD23 Mabs on: 1) eosinophil migration through human umbilical vein endothelial cells (HUVECs); and 2) eosinophil expression of the adhesion molecules leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18), macrophage antigen-1 (Mac-1, CD11b/CD18) and very late activation antigen-1 (VLA-4, CD49d/CD29) was evaluated by specific Mab staining and flow cytometric analysis. As compared to controls, freshly isolated eosinophils from atopic individuals showed enhanced migration through HUVECs (p<0.05) and increased LFA-1 expression (p<0.01), but similar Mac-1 and VLA-4 expression (p>0.1 for both). In both controls and atopic individuals, eosinophil incubation with antihuman CD23 Mabs induced a dose-dependent increase in cell migration through HUVECs, significant at antihuman CD23 Mab concentrations of 5 microg x mL(-1) (p>0.05 for all). Similarly, incubation of the cells with antihuman CD23 Mabs induced dose-dependent upregulation of LFA-1 and Mac-1 expression, whereas no changes in VLA-4 expression were observed (p>0.1). Finally, the enhanced eosinophil migration induced by antihuman CD23 Mab stimulation was significantly inhibited by antihuman LFA-1 (84+/-14% (mean+/-SEM); p<0.01) and VLA-4 Mabs (47+/-15%; p<0.05) but not by antihuman Mac-1 Mabs (p>0.1). In both atopic and control subjects, immunoglobulin E, low-affinity receptor stimulation induces functional changes in eosinophils characterized by increased eosinophil migration associated with enhanced late function antigen-1 and Mac-1 expression.