FIG 7.

Schematic diagram showing a summary of mechanisms and pathways by which a toxic payload can be delivered into an eosinophil via binding to and inducing the internalization of surface Siglec-8. (1) At baseline, Siglec-8 interacts with sialylated cis ligands on the surface of eosinophils that prevent interaction with trans activating ligands. (2) Antibody ligation of Siglec-8 activates signaling from the cytoplasmic motifs of the receptor. Signaling from the ITIM is involved in the induction of endocytosis, which involves actin rearrangement and the activities of tyrosine kinases and PKC. (3) Siglec-8 endocytosis proceeds via both clathrinmediated and lipid raft/caveolae-mediated pathways. (4) Internalized Siglec-8 localizes to the lysosomal compartment. (5) The linker between the cargo and the anti–Siglec-8 antibody is cleaved, and the cargo is released within the eosinophil to exert its effects. Illustration by Jacqueline Schaffer. PKC, Protein kinase C.