Targeting of a conserved epitope in mouse and human GPVI differently affects receptor function
Please always quote using this 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.…
Author: | 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 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Medizinische Fakultät / Institut für Experimentelle Biomedizin | |
Language: | English |
Parent Title (English): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Year of Completion: | 2022 |
Volume: | 23 |
Issue: | 15 |
Article Number: | 8610 |
Source: | International Journal of Molecular Sciences (2022) 23:15, 8610. doi:10.3390/ijms23158610 |
DOI: | https://doi.org/10.3390/ijms23158610 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | JAQ1; glycoprotein VI; platelet activation; platelet inhibition; platelet receptors |
Release Date: | 2023/04/20 |
Date of first Publication: | 2022/08/03 |
EU-Project number / Contract (GA) number: | 766118 |
OpenAIRE: | OpenAIRE |
Open-Access-Publikationsfonds / Förderzeitraum 2022 | |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |