Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function
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 platel...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8610 |
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| author | Stefano Navarro Andreas Starke Johan W. M. Heemskerk Marijke J. E. Kuijpers David Stegner Bernhard Nieswandt |
| author_facet | Stefano Navarro Andreas Starke Johan W. M. Heemskerk Marijke J. E. Kuijpers David Stegner Bernhard Nieswandt |
| author_sort | Stefano Navarro |
| collection | DOAJ |
| description | 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 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 (<i>hGP6<sup>tg/tg</sup></i>). These results indicate that the binding of JAQ1 to a structurally conserved epitope in GPVI differently affects its function in human and mouse platelets. |
| first_indexed | 2024-03-09T05:20:25Z |
| format | Article |
| id | doaj.art-b18a56ac2c034220ab72c95763552f01 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:20:25Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b18a56ac2c034220ab72c95763552f012023-12-03T12:40:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315861010.3390/ijms23158610Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor FunctionStefano Navarro0Andreas Starke1Johan W. M. Heemskerk2Marijke J. E. Kuijpers3David Stegner4Bernhard Nieswandt5Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Integrative and Translational Bioimaging, Josef-Schneider-Straße 2, 97080 Würzburg, GermanyInstitute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Integrative and Translational Bioimaging, Josef-Schneider-Straße 2, 97080 Würzburg, GermanyDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The NetherlandsInstitute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Integrative and Translational Bioimaging, Josef-Schneider-Straße 2, 97080 Würzburg, GermanyInstitute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Integrative and Translational Bioimaging, Josef-Schneider-Straße 2, 97080 Würzburg, GermanyGlycoprotein (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 (<i>hGP6<sup>tg/tg</sup></i>). These results indicate that the binding of JAQ1 to a structurally conserved epitope in GPVI differently affects its function in human and mouse platelets.https://www.mdpi.com/1422-0067/23/15/8610glycoprotein VIJAQ1platelet receptorsplatelet activationplatelet inhibition |
| spellingShingle | Stefano Navarro Andreas Starke Johan W. M. Heemskerk Marijke J. E. Kuijpers David Stegner Bernhard Nieswandt Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function International Journal of Molecular Sciences glycoprotein VI JAQ1 platelet receptors platelet activation platelet inhibition |
| title | Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function |
| title_full | Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function |
| title_fullStr | Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function |
| title_full_unstemmed | Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function |
| title_short | Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function |
| title_sort | targeting of a conserved epitope in mouse and human gpvi differently affects receptor function |
| topic | glycoprotein VI JAQ1 platelet receptors platelet activation platelet inhibition |
| url | https://www.mdpi.com/1422-0067/23/15/8610 |
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