title: Role of Siglec-7 in apoptosis in human platelets.
abstract: BACKGROUND
  Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis.
  
  
  RESULTS
  We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on α granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (ΔΨm) depolarization; (ii) elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii) phosphatidylserine exposure and (iv), microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis.
  
  
  CONCLUSIONS
  The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions), Siglec-7 might be a molecular target for therapeutic intervention/prevention.
authors.affiliation: GIMAP-EA3064, Université de Lyon, Saint-Etienne, France.
authors.forename: Kim Anh
authors.initials: KA
authors.lastname: Nguyen
authors.affiliation: GIMAP-EA3064, Université de Lyon, Saint-Etienne, France.
authors.forename: Hind
authors.initials: H
authors.lastname: Hamzeh-Cognasse
authors.affiliation: 4D Multiphotonic Confocal Microscopy Platform (Hubert Curien Laboratory and UMR CNRS 5516), Université de Lyon, Saint-Etienne, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Palle
authors.affiliation: Centre de Microscopie Electronique Stéphanois - CMES-Saint Etienne, Université de Lyon, Saint-Etienne, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Anselme-Bertrand
authors.affiliation: EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Charles-Antoine
authors.initials: CA
authors.lastname: Arthaud
authors.affiliation: EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Chavarin
authors.affiliation: GIMAP-EA3064, Université de Lyon, Saint-Etienne, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pozzetto
authors.affiliation: GIMAP-EA3064, Université de Lyon, Saint-Etienne, France; EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Garraud
authors.affiliation: GIMAP-EA3064, Université de Lyon, Saint-Etienne, France; EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cognasse
mesh_terms: D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; C402206:SIGLEC7 protein, human