Comparative analysis of the internalization of the macrophage receptor sialoadhesin in human and mouse primary macrophages and cell lines |
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| Affiliation: | 1. Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp (UA), Antwerp 2610, Belgium;2. Laboratory of Cell Biology and Histology, University of Antwerp (UA), Antwerp 2020, Belgium;1. Department of Animal Medicine and Surgery, Faculty of Veterinary Medicine, Universitat Autònoma de Barcelona, Spain;2. Department of Animal Medicine and Surgery, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Spain;3. Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom,;4. Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstrasse 19-21, 50935 Köln, Germany, and;5. Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom;1. Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel;1. Kent Fungal Group, School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK;1. Laboratory of Aquaculture and Artemia Reference Center, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium;2. School of Fisheries and Aquaculture Sciences, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia;3. Department of Pharmaceutics, Faculty of Pharmaceutical Science, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium;4. Laboratory of Immunology and Animal Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium;5. Écloserie Marine de Gravelines, voie des Enrochements, 59820 Gravelines, France |
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| Abstract: | Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs. Such drugs or toxins can be linked to Sn-specific antibodies which should enable their targeted uptake by macrophages. However, the activity of such drugs depends not only on their internalization but also on the intracellular trafficking and final fate in the endolysosomal system. Although information is available for porcine Sn, the detailed mechanisms of human and mouse Sn internalization and subsequent intracellular trafficking are currently unknown. To allow development of Sn-targeted therapies, differences across species and cellular background need to be characterized in more detail. In the current report, we show that internalization of human and mouse Sn is dynamin-dependent and clathrin-mediated, both in primary macrophages and CHO cell lines expressing a recombinant Sn. In primary macrophages, internalized Sn-specific F(ab’)2 fragments are located mostly in the early endosomes. With Fc containing Sn-specific antibodies, there is a slight shift towards lysosomal localization in mouse macrophages, possibly because of an interaction with Fc receptors. Surprisingly, in CHO cell lines expressing Sn, there is a predominant lysosomal localization. Our results show that the mechanism of Sn internalization and intracellular trafficking is concurrent in the tested species. The cellular background in which Sn is expressed and the type of antibody used can affect the intracellular fate, which in turn can impact the activity of antibody-based therapeutic interventions via Sn. |
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| Keywords: | Sialoadhesin/Siglec-1/CD169 Internalization Antibodies |
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