title: Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis.
abstract: The link between platelet activation and vascular injury in Systemic Sclerosis (SSc) is poorly characterized. Here we report that platelet activation results in i) the translocation from the cytoplasm to the surface of HMGB1, a prototypical DAMP signal associated with tissue regeneration and ii) the release of platelet derived microparticles (PDμP) expressing HMGB1. Decreased HMGB1 content (334.6 ± 21.2 vs 587.1 ± 11.1 AUF, P < 0.001) and HMGB1 translocation to the outer leaflet of the plasma membrane (17.8 ± 3.5 vs 4.5 ± 0.5%, P < 0.001) characterize circulating platelets of SSc patients (n = 29) when compared with age-matched healthy controls (HC, n = 20). Conversely, a significantly higher fraction of PDμP in the blood of SSc patients, but not of HC, consistently expose (HMGB1 (MFI 62.8 ± 3.95 vs 4.3 ± 0.7). Platelet HMGB1 depletion is significantly associated in SSc patients with degranulation and with expression of P-selectin and of tissue factor as well as with fibrinogen binding to their plasma membrane. These findings indicate that platelets represent a source of HMGB1, an ancestral signal of necrosis, in the vasculature of SSc patients, possible contributing to persistent microvascular injury and endothelial cell activation.
authors.affiliation: San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Norma
authors.initials: N
authors.lastname: Maugeri
authors.forename: Stefano
authors.initials: S
authors.lastname: Franchini
authors.forename: Lara
authors.initials: L
authors.lastname: Campana
authors.forename: Mattia
authors.initials: M
authors.lastname: Baldini
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Ramirez
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sabbadini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
mesh_terms: D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D015539:Platelet Activation; D021381:Protein Transport; D012595:Scleroderma, Systemic / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D013925:Thromboplastin / Q000276:immunology / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D019007:P-Selectin; D005340:Fibrinogen; D013925:Thromboplastin