Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function.
JAQ1
glycoprotein VI
platelet activation
platelet inhibition
platelet receptors
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
03 Aug 2022
03 Aug 2022
Historique:
received:
07
07
2022
revised:
29
07
2022
accepted:
02
08
2022
entrez:
12
8
2022
pubmed:
13
8
2022
medline:
16
8
2022
Statut:
epublish
Résumé
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 (
Identifiants
pubmed: 35955743
pii: ijms23158610
doi: 10.3390/ijms23158610
pmc: PMC9369317
pii:
doi:
Substances chimiques
Epitopes
0
Platelet Membrane Glycoproteins
0
Collagen
9007-34-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Union's Horizon 2020 research and innovation program under the Marie Slodow-ska-Curie
ID : 766118
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