Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis

Norma Maugeri, Stefano Franchini, Lara Campana, Mattia Baldini, Giuseppe A. Ramirez, Maria Grazia Sabbadini, Patrizia Rovere-Querini, Angelo A. Manfredi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)584-587
Number of pages4
JournalAutoimmunity
Volume45
Issue number8
DOIs
Publication statusPublished - Dec 2012

Keywords

  • HMGB1
  • Innate immunity
  • Platelets
  • Systemic sclerosis
  • Vessel inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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