Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target
Jason S. Knight, … , Daniel T. Eitzman, Amr H. Sawalha
Jason S. Knight, … , Daniel T. Eitzman, Amr H. Sawalha
Published September 21, 2017
Citation Information: JCI Insight. 2017;2(18):e93897. https://doi.org/10.1172/jci.insight.93897.
View: Text | PDF
Research Article

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

  • Text
  • PDF
Abstract

Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils — neutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS.

Authors

Jason S. Knight, He Meng, Patrick Coit, Srilakshmi Yalavarthi, Gautam Sule, Alex A. Gandhi, Robert C. Grenn, Levi F. Mazza, Ramadan A. Ali, Paul Renauer, Jonathan D. Wren, Paula L. Bockenstedt, Hui Wang, Daniel T. Eitzman, Amr H. Sawalha

×

Figure 2

Genes upregulated in APS neutrophils that had been associated with “cell adhesion” within MEDLINE abstracts.

Options: View larger image (or click on image) Download as PowerPoint
Genes upregulated in APS neutrophils that had been associated with “cell...
Genes that had also been associated with “neutrophil adhesion” are shown in blue. The size of each node is proportional to the number of connections within this network, and the thickness of the edges is proportional to the number of times the terms were co-mentioned in the literature. Relationships with a strength of 5 or greater (see Methods) and genes with at least 4 connections within the network were included in the figure. This was done to reduce clutter and emphasize which genes were highly interconnected within the cellular adhesion network.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts