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Title
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Comparative analysis of the internalization of the macrophagereceptor sialoadhesin in human and mouse primary macrophages andcell lines
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Author
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Abstract
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| Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind withsialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal anti-bodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The lattercharacteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the factthat Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entryportal for phenotype-modulating or cytotoxic drugs. Such drugs or toxins can be linked to Sn-specificantibodies which should enable their targeted uptake by macrophages. However, the activity of suchdrugs depends not only on their internalization but also on the intracellular trafficking and final fate inthe endolysosomal system. Although information is available for porcine Sn, the detailed mechanismsof 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 needto be characterized in more detail. In the current report, we show that internalization of human andmouse Sn is dynamin-dependent and clathrin-mediated, both in primary macrophages and CHO celllines expressing a recombinant Sn. In primary macrophages, internalized Sn-specific F(ab)2fragmentsare located mostly in the early endosomes. With Fc containing Sn-specific antibodies, there is a slightshift towards lysosomal localization in mouse macrophages, possibly because of an interaction with Fcreceptors. Surprisingly, in CHO cell lines expressing Sn, there is a predominant lysosomal localization. Ourresults show that the mechanism of Sn internalization and intracellular trafficking is concurrent in thetested species. The cellular background in which Sn is expressed and the type of antibody used can affectthe intracellular fate, which in turn can impact the activity of antibody-based therapeutic interventionsvia Sn. |
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Language
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English
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Source (journal)
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Immunobiology. - Stuttgart, 1979, currens
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Publication
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Jena
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Elsevier gmbh, urban & fischer verlag
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2017
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ISSN
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0171-2985
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DOI
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10.1016/J.IMBIO.2016.11.013
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Volume/pages
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222
:6
(2017)
, p. 797-806
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ISI
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000404314200003
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Pubmed ID
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27899210
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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