Cooperation between Fcγ receptor II and complement receptor type 3 during activation of platelet-activating factor release by cytokine-primed human eosinophils

After priming with cytokines, such as granulocyte-macrophage colony- stimulating factor (GM-CSF), IL-3, or IL-5, eosinophils are stimulated potently by opsonized particles like serum-treated zymosan (STZ), resulting in activation of the respiratory burst and production of lipid mediators, such as platelet-activating factor (PAF) and leukotriene C₄ (LTC₄). In the present study, the role of the opsonin receptors FcγRII and CR3 during both STZ-induced activation of the respiratory burst and PAF release by human eosinophils was investigated. Inhibition studies with blocking mAbs (αbFcγRII: AT10, IV.3; αCR3: B2.12, 44a) showed that both FcγRII and CR3 are important for STZ-induced PAF release by cytokine-primed eosinophils. In contrast, CR3 is involved in activation of the respiratory burst, whereas FcγRII seems not to be important, because blocking anti-FcγRII mAbs had no effect. Subsequently, experiments were performed with zymosan particles coated with IgG, iC3b, or a combination of both. IgG-coated particles poorly activated both responses in GM-CSF primed and unprimed cells. iC3b-Zymosan activated the respiratory burst as well as zymosan expressing both opsonins (IgG/iC3b-zymosan). In contrast, iC3b-zymosan induced significantly less PAF release by GM-CSF-primed eosinophils than did IgG/iC3b-zymosan, suggesting synergism between FcγRII and CR3. This synergistic effect was not observed when IgG-zymosan and iC3b-zymosan were added simultaneously. Therefore, these data indicate that on human eosinophils, FcγRII and CR3 act synergistically to activate PAF release, provided that their ligands are in close proximity.