title: Differential activation of human platelets induced by Fc gamma receptor II cross-linking and by anti-CD9 monoclonal antibody.
abstract: Platelet activation induced by anti-CD9 mAb, which depends upon Fc gammaRII, has been considered to be similar to that induced by Fc gammaRII cross-linking. In this work, we present several lines of evidence to suggest that the mode of platelet activation induced by anti-CD9 mAb is distinct from that induced by Fc gammaRII cross-linking. Ca2+ release from intracellular Ca2+ stores induced by anti-CD9 mAb depended almost totally upon thromboxane A2 production and released ADP, whereas that induced by Fc gammaRII was affected only minimally by these factors. Fc gammaRII cross-linking induced Ca2+ channel opening, which is dependent upon the depletion of intracellular Ca2+ stores. In contrast, anti-CD9 mAb appeared to directly open Ca2+ channels, irrespective of intracellular Ca2+ stores (Kuroda et al., 1995. J. Immunol. 155: 4427). The Ca2+ requirement for the Ca2+ channels opened by Fc gammaRII cross-linking was also distinct from that induced by anti-CD9 mAb. The early phase of Fc gammaRII tyrosine phosphorylation was dependent upon thromboxane A2 production with anti-CD9 mAb-induced activation, whereas that of Fc gammaRII cross-linking was not. p72(syk) and p53/56(lyn) appeared to associate with Fc gammaRII in platelet activation induced by Fc gammaRII cross-linking, whereas there was little, if any, association between Fc gammaRII and these tyrosine kinases in anti-CD9 mAb-induced activation. Piceatannol, a selective inhibitor of p72(syk), enhanced Fc gammaRII tyrosine phosphorylation induced by Fc gammaRII cross-linking, whereas it attenuated the process in anti-CD9 mAb-induced platelet activation. It is suggested that the regulatory mechanism of Fc gammaRII tyrosine phosphorylation differs between these two modes of platelet activation.
authors.affiliation: Department of Clinical and Laboratory Medicine, Yamanashi Medical University, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Qi
authors.forename: Y
authors.initials: Y
authors.lastname: Ozaki
authors.forename: K
authors.initials: K
authors.lastname: Kuroda
authors.forename: N
authors.initials: N
authors.lastname: Asazuma
authors.forename: Y
authors.initials: Y
authors.lastname: Yatomi
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: S
authors.initials: S
authors.lastname: Kume
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D015539:Platelet Activation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011940:Receptor Aggregation; D017452:Receptors, IgG / Q000502:physiology*; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D000072377:Syk Kinase; D060245:Tetraspanin 29
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554869:CD9 protein, human; D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D017452:Receptors, IgG; D013267:Stilbenes; D060245:Tetraspanin 29; D019000:Phosphotyrosine; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D002118:Calcium