Targeting of a conserved epitope in mouse and human GPVI differently affects receptor function
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-286227
- Glycoprotein (GP) VI is the major platelet collagen receptor and a promising anti-thrombotic target. This was first demonstrated in mice using the rat monoclonal antibody JAQ1, which completely blocks the Collagen-Related Peptide (CRP)-binding site on mouse GPVI and efficiently inhibits mouse platelet adhesion, activation and aggregation on collagen. Here, we show for the first time that JAQ1 cross-reacts with human GPVI (huGPVI), but not with GPVI in other tested species, including rat, rabbit, guinea pig, swine, and dog. We furtherGlycoprotein (GP) VI is the major platelet collagen receptor and a promising anti-thrombotic target. This was first demonstrated in mice using the rat monoclonal antibody JAQ1, which completely blocks the Collagen-Related Peptide (CRP)-binding site on mouse GPVI and efficiently inhibits mouse platelet adhesion, activation and aggregation on collagen. Here, we show for the first time that JAQ1 cross-reacts with human GPVI (huGPVI), but not with GPVI in other tested species, including rat, rabbit, guinea pig, swine, and dog. We further demonstrate that JAQ1 differently modulates mouse and human GPVI function. Similar to its effects on mouse GPVI (mGPVI), JAQ1 inhibits CRP-induced activation in human platelets, whereas, in stark contrast to mouse GPVI, it does not inhibit the adhesion, activation or aggregate formation of human platelets on collagen, but causes instead an increased response. This effect was also seen with platelets from newly generated human GPVI knockin mice (hGP6\(^{tg/tg\)). These results indicate that the binding of JAQ1 to a structurally conserved epitope in GPVI differently affects its function in human and mouse platelets.…
Autor(en): | Stefano Navarro, Andreas Starke, Johan W. M. Heemskerk, Marijke J. E. Kuijpers, David Stegner, Bernhard Nieswandt |
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URN: | urn:nbn:de:bvb:20-opus-286227 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Medizinische Fakultät / Institut für Experimentelle Biomedizin | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 23 |
Heft / Ausgabe: | 15 |
Aufsatznummer: | 8610 |
Originalveröffentlichung / Quelle: | International Journal of Molecular Sciences (2022) 23:15, 8610. doi:10.3390/ijms23158610 |
DOI: | https://doi.org/10.3390/ijms23158610 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | JAQ1; glycoprotein VI; platelet activation; platelet inhibition; platelet receptors |
Datum der Freischaltung: | 20.04.2023 |
Datum der Erstveröffentlichung: | 03.08.2022 |
EU-Projektnummer / Contract (GA) number: | 766118 |
OpenAIRE: | OpenAIRE |
Open-Access-Publikationsfonds / Förderzeitraum 2022 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |