title: The CD47 pathway is deregulated in human immune thrombocytopenia.
abstract: OBJECTIVE
  A novel mechanism of platelet destruction involving the CD47/ signal regulatory protein-α (SIRPα) system has recently been suggested in a mouse model of immune thrombocytopenia (ITP). The CD47 molecule serves as ligand for SIRPα receptor and as receptor for thrombospondin acting as antagonistic to phagocyte activity and a regulator of apoptosis, respectively. In this study, we evaluated if the CD47/SIRPα axis may be involved in the apoptosis and clearance of platelets in human ITP.
  
  
  METHODS
  Using flow cytometry, we characterized whether expression of CD47 on fresh and in vitro-aged platelets- and of SIRPα receptor on CD14-derived dendritic cells (DCs), macrophages, circulating DCs, and monocytes is reduced is ITP; whether the in vitro platelet phagocytic capacity of CD14-derived DCs and macrophages is differentially modulated in the presence or absence of antibodies against CD47 and SIRPα in ITP; and whether platelets are more susceptible to the CD47-induced death signal in ITP.
  
  
  RESULTS
  We demonstrated that low platelet count in ITP is not due to increased phagocytosis associated with decreased expression of CD47 on the platelet surface and, despite reduced SIRPα expression, blockage of SIRPα on immature CD14-derived DCs or CD47 on platelets by specific antibodies failed to modify platelet uptake/phagocytosis of DCs. In contrast, targeting platelet CD47 with specific antibody significantly increases platelet phagocytosis of CD14-derived macrophages, and platelets are not healthy because they show increased apoptosis and are resistant to CD47-induced death signal.
  
  
  CONCLUSIONS
  Our results demonstrate that the CD47 pathway in ITP patients abnormally modulates platelet homeostasis.
authors.affiliation: Department of Hematology and Oncological Sciences L. & A. Seràgnoli, Institute of Hematology, University of Bologna, Bologna, Italy. lucia.catani@unibo.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Catani
authors.forename: Daria
authors.initials: D
authors.lastname: Sollazzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.forename: Nicola
authors.initials: N
authors.lastname: Polverelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Palandri
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Nicola
authors.initials: N
authors.lastname: Vianelli
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lemoli
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D051928:CD47 Antigen / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology*; D019700:Thrombospondin 1 / Q000097:blood / Q000276:immunology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000906:Antibodies; D000943:Antigens, Differentiation; D051928:CD47 Antigen; D018950:Lipopolysaccharide Receptors; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D019700:Thrombospondin 1