COOPERATION BETWEEN FC-GAMMA 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-st imulating factor (CM-CSF), IL-3, or IL-5, eosinophils are stimulated p otently by opsonized particles like serum-treated zymosan (STZ), resul ting in activation of the respiratory burst and production of lipid me diators, such as platelet-activating factor (PAF) and leukotriene C-4 (LTC(4)). In the present study, the role of the opsonin receptors Fc g amma RII and CR3 during both STZ-induced activation of the respiratory burst and PAF release by human eosinophils was investigated. Inhibiti on studies with blocking mAbs (alpha hFc gamma RII: AT10, IV.3; alpha CR3: B2.12, 44a) showed that both Fc gamma RII and CR3 are important f or STZ-induced PAF release by cytokine-primed eosinophils. In contrast , CR3 is involved in activation of the respiratory burst, whereas Fc g amma RII seems not to be important, because blocking anti-Fc gamma RII mAbs had no effect. Subsequently, experiments were performed with zym osan particles coated with IgG, iC3b, or a combination of both. IgG-co ated particles poorly activated both responses in GM-CSF primed and un primed cells. iC3b-Zymosan activated the respiratory burst as well as zymosan expressing both opsonins (IgC/iC3b-zymosan). In contrast, iC3b -zymosan induced significantly less PAF release by CM-CSF-primed eosin ophils than did IgC/iC3b-zymosan, suggesting synergism between Fc gamm a RII and CR3. This synergistic effect was not observed when Igc-zymos an and iC3b-zymosan were added simultaneously. Therefore, these data i ndicate that on human eosinophils, Fc gamma RII and CR3 act synergisti cally to activate PAF release, provided that their ligands ape in clos e proximity.