Platelet internalization in early thrombogenesis.

Abstract

Activated platelets rapidly internalize ligand-alpha(IIb)beta 3 complexes and particulates. The platelets sequester these primarily to the surface-connected canalicular system (SCCS), alpha-granules or evaginated surfaces. This occurs swiftly as activation initiates shape change, internal transformation, and secretion out of the platelet SCCS. The transmembrane signaling mechanism for internalization is through the platelet submembranous, detergent-resistant, cytochalasin B-resistant cytoskeletal filaments, not cytoplasmic actin filaments. This work proposes the model that platelet internalization responses contribute in the retraction of clots and participate in vivo in thrombus development at sites of coronary artery injury. In isometric clot retraction, the retracting platelets show internalization of fibrinogen-gold and fibrin while spreading on the polymerizing fibrin strands. The combination of platelet internalization (retracting) with evagination (spreading) on fibrin strands appear to approximate and organize nearby platelets into the developing thrombi. Ex vivo findings are similar under flowing conditions on denuded rabbit aortic endothelium with fibrinogen-gold markers. Early thrombi developing in vivo at sites of congenital coronary artery lesions in perinatal piglets show fibrin strands internalized into the SCCS of platelets. A thrombogenesis model is proposed that shows that platelet internalization responses anchor fibrin and approximate platelets, thus enhancing thrombus development and retraction.