Use of a conditional Glanzmann thrombasthenia mouse model reveals a supportive and possibly non-adhesive role for TLT-1 in the platelet-fibrinogen interaction

利用条件性格氏血小板无力症小鼠模型揭示了TLT-1在血小板-纤维蛋白原相互作用中发挥支持作用,且可能不发挥黏附作用。

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Abstract

The platelet integrin receptor, αIIbβ3, binds fibrinogen to mediate platelet-platelet contacts, regulate hemostasis, and modulate inflammation. The Triggering Receptor Expressed in Myeloid (TREM) - Like (TLT)-1 is an enigmatic 34kD receptor found on platelets that affects their hemostatic and inflammatory functions. Similar to αIIbβ3, TLT-1's ligand is also fibrinogen; however, TLT-1's direct role in platelet function remains unknown. We created a tamoxifen-inducible conditional αIIb deficient ((c)Itga2b(-/-)) mouse to better understand TLT-1's role in platelet function, specifically TLT-1's binding to fibrinogen and its role in hemostasis and inflammation. We first characterized our (c)Itga2b(-/-) null mouse and subsequently crossed this mouse with a Treml1(-/-) mouse, creating a conditional double knockout ((c)DKO). While the floxed (c)Itga2b /Treml1(-/-) mouse shows significant differences compared to control mice, deleting Treml1 from the (c)Itga2b(-/-) mouse results in only minor differences from the (c)Itga2b(-/-) strain in bleeding, aggregation, fibrinogen deposition and platelet spreading assays. Our data suggest that while TLT-1 plays a visible role in hemostasis, it primarily supports aggregation but may not function as an adhesive component.

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