title: Contact- and agonist-regulated microvesiculation of human platelets.
abstract: After exposure to an agonist, platelets are activated and become aggregated. They also shed membrane microparticles that participate in the pathogenesis of thrombosis, hyper-coagulation and inflammation. However, microvesiculation can potentially disrupt the integrity of platelet aggregation by shedding the membrane receptors and phosphatidylserine critical for forming and stabilising a platelet clot. We tested the hypothesis that adhesion and microvesiculation are functions of different subsets of platelets at the time of haemostasis by real-time monitoring of agonist-induced morphological changes and microvesiculation of human platelets.We identified two types of platelets that are adherent to fibrinogen: a high density bubble shape (HDBS) and low-density spread shape (LDSS). Adenosine diphosphate (ADP) predominantly induced HDBS platelets to vesiculate, whereas LDSS platelets were highly resistant to such vesiculation. Thrombin-receptor activating peptide (TRAP) stabilised platelets against microvesiculation by promoting a rapid HDBS-to-LDSS morphological transition. These activities of ADP and TRAP were reversed for platelets in suspension, independent of an engagement integrin αIIbβ3. As the result of membrane contact, LDSS platelets inhibited the microvesiculation of HDBS platelets in response to ADP. Aspirin and clopidogrel inhibited ADP-induced microvesiculation through different mechanisms. These results suggest that platelet aggregation and microvesiculation occur in different subsets of platelets and are differently regulated by agonists, platelet-platelets and platelet-fibrinogen interactions.
authors.affiliation: Department of Neurosurgery, University General Hospital, Tianjin Medical University, 154 Anshan Road, Tianjin, China. jianningzhang@hotmail.com
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Zaske
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Fu
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Conyers
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Jing-fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000244:Adenosine Diphosphate / Q000097:blood / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000648:ultrastructure; D000077144:Clopidogrel; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C086309:thrombin receptor peptide SFLLRNP; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin