CLEC-2 supports platelet aggregation in mouse but not human blood at arterial shear

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 GPIb-Cre recombinase mouse for more restricted deletion of platelet-CLEC-2 than the previously used PF4-Cre mouse. CLEC1bfl/flGPIb-Cre+ mice are born at Mendelian ratio, with a mild reduction in platelet count, and present with reduced thrombus size post-FeCl3-induced thrombosis, compared to littermates. Antibody-mediated depletion of platelet count in C57BL/6 mice, to match CLEC1bfl/flGPIb-Cre+ mice, revealed that the reduced thrombus size post-FeCl3-injury was due to the loss of CLEC-2, and not mild thrombocytopenia. Similarly, CLEC1bfl/flGPIb-Cre+ mouse blood replenished with CLEC-2-deficient platelets ex vivo 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 CLEC1bfl/flGPIb-Cre+ 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.

Object Details

• Alternative title: CLEC-2 in platelet aggregation
• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: CLEC-2 supports platelet aggregation in mouse but not human blood at arterial shear ; day:11 ; month:07 ; year:2022 ; Thrombosis and haemostasis ; (11.07.2022)

Contributors, Places and Time

• Contributor: Bourne, Joshua ; Smith, Christopher ; Jooss, Natalie ; Di, Ying ; Brown, Helena ; Montague, Samantha ; Thomas, Mark ; Poulter, Natalie ; Rayes, Julie ; Watson, Steve P.

Further information

• DOI: 10.1055/a-1896-6992
• URN: urn:nbn:de:101:1-2022101017240934356007
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:39 AM CEST