作者: Marjorie De Schryver , Annelies Leemans , Isabel Pintelon , Davie Cappoen , Louis Maes
DOI: 10.1016/J.IMBIO.2016.11.013
关键词: Monoclonal antibody 、 Intracellular 、 Internalization 、 Downregulation and upregulation 、 Sialoadhesin 、 Macrophage 、 Endosome 、 Biology 、 Receptor 、 Cell biology
摘要: Abstract Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind sialic acids. During inflammation, an upregulation of Sn observed. Upon binding monoclonal antibodies Sn, becomes internalized and this has been observed in multiple species. The latter characteristic, combined strong inflammatory fact that Sn-positive contribute certain diseases, makes interesting entry portal for phenotype-modulating or cytotoxic drugs. Such drugs toxins can be linked Sn-specific which should enable their targeted uptake by macrophages. However, activity such depends not only internalization but also intracellular trafficking final fate endolysosomal system. Although information available porcine detailed mechanisms human mouse subsequent are currently unknown. To allow development Sn-targeted therapies, differences across species cellular background need characterized more detail. In current report, we show dynamin-dependent clathrin-mediated, both primary CHO cell lines expressing recombinant Sn. macrophages, F(ab’) 2 fragments located mostly early endosomes. With Fc containing antibodies, there slight shift towards lysosomal localization possibly because interaction receptors. Surprisingly, predominant localization. Our results mechanism concurrent tested type antibody used affect fate, turn impact antibody-based therapeutic interventions via