{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bourne JH"],"funding":["Marie Sklodowska-Curie Actions","British Heart Foundation","FS/IBSRF/20/25039","766118","CH/03/003","AA/18/2/34218"],"pagination":["1988-2000"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9718592"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(12)"],"pubmed_abstract":["C-type lectin-like receptor 2 (CLEC-2) is highly expressed on platelets and a subpopulation of myeloid cells, and is critical in lymphatic development. CLEC-2 has been shown to support thrombus formation at sites of inflammation, but to have a minor/negligible role in hemostasis. This identifies CLEC-2 as a promising therapeutic target in thromboinflammatory disorders, without hemostatic detriment. We utilized a GPIbα-Cre recombinase mouse for more restricted deletion of platelet-CLEC-2 than the previously used PF4-Cre mouse. clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mice are born at a Mendelian ratio, with a mild reduction in platelet count, and present with reduced thrombus size post-FeCl<sub>3</sub>-induced thrombosis, compared to littermates. Antibody-mediated depletion of platelet count in C57BL/6 mice, to match clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mice, revealed that the reduced thrombus size post-FeCl<sub>3</sub>-injury was due to the loss of CLEC-2, and not mild thrombocytopenia. Similarly, clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mouse blood replenished with CLEC-2-deficient platelets <i>ex vivo</i> to match littermates had reduced aggregate formation when perfused over collagen at arterial flow rates. In contrast, platelet-rich thrombi formed following perfusion of human blood under flow conditions over collagen types I or III, atherosclerotic plaque, or inflammatory endothelial cells were unaltered in the presence of CLEC-2-blocking antibody, AYP1, or recombinant CLEC-2-Fc. The reduction in platelet aggregation observed in clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mice during arterial thrombosis is mediated by the loss of CLEC-2 on mouse platelets. In contrast, CLEC-2 does not support thrombus generation on collagen, atherosclerotic plaque, or inflamed endothelial cells in human at arterial shear."],"journal":["Thrombosis and haemostasis"],"pubmed_title":["CLEC-2 Supports Platelet Aggregation in Mouse but not Human Blood at Arterial Shear."],"pmcid":["PMC9718592"],"funding_grant_id":["Marie Sklodowska-Curie Actions","British Heart Foundation","FS/IBSRF/20/25039","CH/03/003/15571","766118","CH/03/003","AA/18/2/34218"],"pubmed_authors":["Poulter NS","Watson SP","Bourne JH","Brown HC","Smith CW","Montague SJ","Di Y","Jooss NJ","Thomas MR","Rayes J"],"additional_accession":[]},"is_claimable":false,"name":"CLEC-2 Supports Platelet Aggregation in Mouse but not Human Blood at Arterial Shear.","description":"C-type lectin-like receptor 2 (CLEC-2) is highly expressed on platelets and a subpopulation of myeloid cells, and is critical in lymphatic development. CLEC-2 has been shown to support thrombus formation at sites of inflammation, but to have a minor/negligible role in hemostasis. This identifies CLEC-2 as a promising therapeutic target in thromboinflammatory disorders, without hemostatic detriment. We utilized a GPIbα-Cre recombinase mouse for more restricted deletion of platelet-CLEC-2 than the previously used PF4-Cre mouse. clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mice are born at a Mendelian ratio, with a mild reduction in platelet count, and present with reduced thrombus size post-FeCl<sub>3</sub>-induced thrombosis, compared to littermates. Antibody-mediated depletion of platelet count in C57BL/6 mice, to match clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mice, revealed that the reduced thrombus size post-FeCl<sub>3</sub>-injury was due to the loss of CLEC-2, and not mild thrombocytopenia. Similarly, clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mouse blood replenished with CLEC-2-deficient platelets <i>ex vivo</i> to match littermates had reduced aggregate formation when perfused over collagen at arterial flow rates. In contrast, platelet-rich thrombi formed following perfusion of human blood under flow conditions over collagen types I or III, atherosclerotic plaque, or inflammatory endothelial cells were unaltered in the presence of CLEC-2-blocking antibody, AYP1, or recombinant CLEC-2-Fc. The reduction in platelet aggregation observed in clec1b<sup>fl/fl</sup>GPIbα-Cre<sup>+</sup> mice during arterial thrombosis is mediated by the loss of CLEC-2 on mouse platelets. In contrast, CLEC-2 does not support thrombus generation on collagen, atherosclerotic plaque, or inflamed endothelial cells in human at arterial shear.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-19T17:28:41.247Z","creation":"2025-04-19T17:28:41.247Z"},"accession":"S-EPMC9718592","cross_references":{"pubmed":["35817083"],"doi":["10.1055/a-1896-6992"]}}