Presentation Highlights

During Thursday morning’s “Platelets and Inflammation” Oral Communications Session, Robert Campbell, Ph.D., presented his findings on interferon-induced transmembrane 3, or IFITM3—an interferon responsive gene product that restricts pathogen replication. Campbell and colleagues investigated the role of IFITM3 in platelets and megakaryocytes (MKs):

  • Upon interferon-α (IFNα) stimulation in vitro, IFITM3 surface expression and fibrinogen (Fgn) endocytosis in MKs significantly increased.
  • In wild-type mice, IFNα stimulated platelet fibrinogen endocytosis, αIIbβ3 activation, platelet aggregation, and death from thrombosis. Ifitm-/- mice were protected from IFN-induced platelet hyperreactivity and thrombosis.
  • Platelets from patients with systemic inflammation mirrored findings in murine models with increased IFITM3 expression, αIIbβ3 expression, Fgn content, and aggregation.

These findings suggest that IFITM3 is a novel regulator of MK and platelet Fgn endocytosis under inflammatory stimuli, and is necessary for IFN-induced platelet hyperreactivity and thrombosis.


Until now, the interaction of IFITM3, an interferon (IFN) regulated gene product which restricts pathogen replication through vesicular trafficking mechanisms, has not been examined in megakaryocytes (MKs) and platelets. This study reported the expression, regulation, and function of IFITM3 in MKs and platelets under inflammatory conditions.

Cultured murine MKs were stimulated or not with IFNα. IFITM3 expression and localization were determined in MKs and developing proplatelets. Fibrinogen (Fgn) endocytosis, a clathrin-mediated event requiring integrin αIIbβ3, was measured in IFN-stimulated MKs and platelets from wild type (WT) and Ifitm-/- mice. αIIbβ3 activation, platelet aggregation, and thrombosis was determined in WT and Ifitm-/- mice basally and upon IFN-stimulation. Co-immunoprecipitation identified putative interaction partners for IFITM3.

Upon IFNα stimulation in vitro, IFITM3 surface expression and Fgn endocytosis in MKs increased significantly. Super-resolution microscopy demonstrated that IFITM3 co-localized with αIIbβ3. IFNα stimulation in vivo concordantly increased platelet Fgn endocytosis, platelet aggregation, and death from thrombosis in WT mice. In contrast, Ifitm-/- mice were completely rescued from IFN-induced platelet hyperreactivity and thrombosis (p< 0.05 vs. WT for all comparisons). Clathrin and αIIb were confirmed to closely interact with IFITM3.

IFITM3 expression, Fgn content, and platelet aggregation was also measured in platelets from patients with systemic inflammation and healthy control subjects. Platelets from patients with systemic inflammation mirrored findings in murine models, with significant increases in IFITM3 expression (~20-fold increase in protein), αIIbβ3 expression, Fgn content, and aggregation.

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