Dextran sulfate triggers platelet aggregation via direct activation of PEAR1

The platelet surface receptor, responsible for the DxS-induced Syk-independent Akt-activation, has hitherto not been identified. We found that DxS elicited a concentration-dependent aggregation of human platelets resulting from direct PEAR1 activation by DxS.

Blocking the PEAR1 receptor, in combination with a selective Syk-inhibitor, completely abrogated the DxS-driven platelet aggregation. The DxS-induced Syk-phosphorylation was not affected in Pear1 −/− platelets, but Akt-phosphorylation was largely abolished. As a result, the aggregation of Pear1 −/− platelets was reduced and reversible, i.e. aggregates were less stable compared to wild-type platelet aggregates.