Frontline Science: Superior mouse eosinophil depletion in vivo targeting transgenic Siglec-8 instead of endogenous Siglec-F: Mechanisms and pitfalls.

Journal of Leukocyte Biology
Eva KnuplezBruce S Bochner

Abstract

Eosinophils are important multifunctional granulocytes. When studying eosinophil function and its contribution to diseases, mouse models are often used. Mouse eosinophils selectively express sialic acid-binding immunoglobulin-like lectin (Siglec)-F. Its closest functional paralog on human eosinophils is Siglec-8. These Siglecs are being used to target eosinophils when exploring their mechanistic roles in disease and for potential therapeutic benefit. In order to facilitate preclinical studies of human Siglec-8, we developed transgenic mouse strains expressing human Siglec-8 only on the surface of eosinophils with or without endogenous Siglec-F and have begun characterizing various cellular functions in vitro and in vivo. Eosinophils from Siglec-8+ mice, with or without Siglec-F, responded to Siglec-8 antibody engagement in vitro by up-regulating surface CD11b, whereas Siglec-F antibody had no such effect. Engagement of Siglec-F or Siglec-8 with respective antibodies in vitro resulted in only modest increases in cell death. Administration of rat Siglec-F antibodies to mice led to a significant decrease in Siglec-F surface expression on eosinophils due to internalization, and thus appeared to decrease eosinophil numbers based on ...Continue Reading

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Citations

Sep 15, 2020·Oncoimmunology·Melanie KienzlRudolf Schicho
Aug 9, 2020·Scientific Reports·James D HernandezEleanna De Filippis
Jun 20, 2020·Journal of Leukocyte Biology·Elizabeth A Jacobsen
Dec 31, 2020·Cells·Bradford A YoungbloodBruce S Bochner
Mar 23, 2021·The Journal of Allergy and Clinical Immunology·Jason GotlibCem Akin
Mar 2, 2021·Annual Review of Immunology·Elizabeth A JacobsenMarc E Rothenberg

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