title: Mitochondria regulate platelet metamorphosis induced by opsonized zymosan A--activation and long-term commitment to cell death.
abstract: Changes in the mitochondrial membrane potential play a key role in determining cell fate. Mitochondria membrane hyperpolarization has been found to occur after cell activation, e.g. in lymphocytes, whereas depolarization is associated with apoptosis. The aim of this study was to investigate the effects of an immunological stimulus, i.e. opsonized zymosan A, on human platelet mitochondria by means of flow and static cytometry analyses as well as biochemical methods. We found that opsonized zymosan induced significant changes of platelet morphology at early time points (90 min). This was associated with increased production of reactive oxygen species, and, intriguingly, mitochondrial membrane hyperpolarization. At a later time point (24 h), opsonized zymosan was found to induce increased expression of CD47 adhesion molecule, platelet aggregation, mitochondrial membrane depolarization and phosphatidylserine externalization. Although these late events usually represent signs of apoptosis in nucleated cells, in opsonized zymosan-treated platelets they were not associated with membrane integrity loss, changes in Bcl-2 family protein expression or caspase activation. In addition, pre-treatment with low doses of the 'mitochondriotropic' protonophore carbonyl cyanide p-(trifluoro-methoxy)phenylhydrazone counteracted mitochondrial membrane potential alterations, production of reactive oxygen species and phosphatidylserine externalization induced by opsonized zymosan. Our data suggest that mitochondrial hyperpolarization represents a key event in platelet activation and remodeling under opsonized zymosan immunological stimulation, and opsonized zymosan immunological stimulation may represent a useful tool for understanding of the pathogenetic role of platelet alterations associated with vascular complications occurring in metabolic and autoimmune diseases.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanita', Rome, Italy. paola.matarrese@iss.it
authors.forename: Paola
authors.initials: P
authors.lastname: Matarrese
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Straface
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palumbo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Anselmi
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Gambardella
authors.forename: Barbara
authors.initials: B
authors.lastname: Ascione
authors.forename: Domenico
authors.initials: D
authors.lastname: Del Principe
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
mesh_terms: D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D048430:Cell Shape; D004789:Enzyme Activation; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015054:Zymosan / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D015054:Zymosan; D020169:Caspases