Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis

E Nutku, H Aizawa, SA Hudson, BS Bochner - Blood, 2003 - ashpublications.org
E Nutku, H Aizawa, SA Hudson, BS Bochner
Blood, 2003ashpublications.org
Sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), which exists in 2 isoforms
including one possessing cytoplasmic tyrosine motifs, is expressed only on human
eosinophils, basophils, and mast cells. Until now, its function was unknown. Here we define
a novel function of Siglec-8 on eosinophils. Siglec-8 cross-linking with antibodies rapidly
generated caspase-3–like activity and reduced eosinophil viability through induction of
apoptosis. The pancaspase inhibitor benzyloxycarbonyl (Cbz)–Val-Ala-Asp-(Ome) …
Abstract
Sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), which exists in 2 isoforms including one possessing cytoplasmic tyrosine motifs, is expressed only on human eosinophils, basophils, and mast cells. Until now, its function was unknown. Here we define a novel function of Siglec-8 on eosinophils. Siglec-8 cross-linking with antibodies rapidly generated caspase-3–like activity and reduced eosinophil viability through induction of apoptosis. The pancaspase inhibitor benzyloxycarbonyl (Cbz)–Val-Ala-Asp-(Ome)-fluoromethyl ketone (zVAD-FMK) completely blocked this response, implicating caspases in Siglec-8 cross-linking–induced apoptosis. Eosinophil survival-promoting cytokines such as interleukin 5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) failed to block apoptosis and instead enhanced the sensitivity of eosinophils to undergo apoptosis in response to Siglec-8 antibody. Siglec-8 activation may provide a useful therapeutic approach to reduce numbers of eosinophils (and perhaps basophils and mast cells) in disease states where these cells are important.
ashpublications.org