EOSINOPHIL GRANULOCYTE INTERACTION WITH SERUM-OPSONIZED PARTICLES - BINDING AND DEGRANULATION ARE ENHANCED BY TUMOR-NECROSIS-FACTOR-ALPHA

Eosinophils participate in the inflammatory response seen in allergy a nd helmin thic infestation. Their release of granule-bound cationic pr oteins may play a role in these diseases. Therefore, we investigated m echanisms involved in the release of eosinophil cationic protein (ECP) . Serum-opsonized zymosan was phagocytosed by eosinophils, and ECP was released into the phagosomes as judged by immunoelectron microscopy. Degranulation to the external milieu was induced by serum-opsonized, n on-phagocytosable Sephadex beads (SOS), and ECP release was determined by use of an enzyme-linked immunosorbent assay. CD11b, CD18, and CD32 monoclonal antibodies inhibited degranulation, demonstrating dependen ce on complement receptor type 3 (CR3), and the low-affinity Fc recept or for IgG. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (I L)-5 both rapidly enhanced the binding of eosinophils to serum-opsoniz ed zymosan, and also the release of ECP upon interaction with SOS. The cytokine-induced increase in ECP release was inhibited by the phospho lipase A(2) (PLA(2)) inhibitor mepacrine, indicating an involvement of PLA(2) in the enhanced response but not in baseline degranulation. Au tocrine stimulation by the platelet-activating factor (PAF) is unlikel y since the PAF receptor antagonist WEB 2086 did not inhibit the enhan ced response. In conclusion, the main signals for eosinophil degranula tion on serum-opsonized particles are mediated by CR3 and receptors fo r immunoglobulins. As for IL-5, TNF-alpha changes eosinophil phenotype from a resting to an activated state.