title: Phosphatidylserine exposure and other apoptotic-like events in Bernard-Soulier syndrome platelets.
abstract: In the Bernard-Soulier syndrome (BSS), the giant platelets are said to have increased phosphatidylserine (PS) surface exposure in the resting state and shortened survival in the circulation. When normal platelets are activated, they undergo many biochemical and morphological changes, some of which are apoptotic. Herein, we investigated apoptotic-like events in BSS platelets upon activation, specifically, PS exposure, microparticle (MP) formation, cell shrinkage, and loss of mitochondrial inner membrane potential (DeltaPsi(m)). Platelets from two unrelated BSS patients were examined in whole blood; agonists used were collagen, thrombin, PAR1- or PAR4-activating peptides (APs), or combinations of collagen with thrombin, and the PAR-APs. Flow cytometry was used to measure PS exposure (annexin A5 binding), platelet-derived MPs (forward scatter; events <0.75 microm size), and DeltaPsi(m) (TMRM fluorescence). PS exposure was increased on resting and activated BSS platelets, and this was independent of the platelet size. MP formation by BSS platelets was generally enhanced. Cell shrinkage occurred on activation to form smaller, PS-exposing platelets in BSS and controls. A proportion of PS-exposing BSS and control platelets exhibited DeltaPsi(m) loss, but unlike controls, there was also loss of DeltaPsi(m) in the BSS platelets not exposing PS. Thus, BSS platelets undergo apoptotic-like events upon activation, with PS exposure and MP formation being enhanced. These events may play a role in the shortened survival in BSS, as well as affecting thrombin generation.
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada. margaret.rand@sickkids.ca
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Rand
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: K W Annie
authors.initials: KW
authors.lastname: Bang
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Teitel
authors.forename: Victor S
authors.initials: VS
authors.lastname: Blanchette
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D001606:Bernard-Soulier Syndrome / Q000097:blood*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D048429:Cell Size; D002648:Child; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D008563:Membrane Lipids / Q000097:blood*; D009842:Oligopeptides / Q000096:biosynthesis / Q000494:pharmacology; D010718:Phosphatidylserines / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics; D044463:Receptor, PAR-1 / Q000187:drug effects; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D009842:Oligopeptides; C462999:PAR-1-activating peptide; D010718:Phosphatidylserines; D019038:Platelet Glycoprotein GPIb-IX Complex; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C094990:adhesion receptor; D003094:Collagen; C112908:protease-activated receptor 4