Toll-like receptor and antiphospholipid mediated thrombosis: In vivo studies

Silvia S. Pierangeli, Mariano E. Vega-Ostertag, Elena Raschi, Xiaowei Liu, Zurina Romay-Penabad, Valeria De Micheli, Monica Galli, Marco Moia, Angela Tincani, Maria Orietta Borghi, Tracy Nguyen-Oghalai, Pier Luigi Meroni

Research output: Contribution to journalArticle

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Abstract

Objective: A study was undertaken to investigate the in vivo pathogenic role of Toll-like receptor 4 (TLR-4) in the antiphospholipid syndrome (APS) by studying the thrombogenic antiphospholipid (aPL) activity in lipopolysaccharide (LPS) non-responsive (LPS-/-) mice and the association between tlr4 gene polymorphisms and APS in patients. Methods: IgGs from two patients with APS, one with aPL negative systemic lupus erythematosus (SLE) and one with normal human serum (NHS), were evaluated for thrombosis, tissue factor (TF) activity and endothelial cell activation in LPS-/- mice displaying a tlr4 spontaneous mutation vs LPS responsive (LPS+/+) mice. Human tlr4 Asp299Gly and Thr399Ile polymorphisms were evaluated by allele-specific PCR in 110 patients with APS with arterial/venous thrombosis and in 220 controls of the same ethnic origin. Results: IgG-APS produced significantly larger thrombi and more leucocytes (WBC) adhering to endothelial cells in the cremaster muscle microcirculation of LPS+/+ mice than IgG-NHS or aPL negative SLE-IgG. These effects were abrogated after absorption of the anti-β2glycoprotein I activity by an affinity column. The two IgG-APS induced significantly smaller thrombi and fewer WBC adhering to endothelial cells in LPS-/- mice than in LPS+/+ mice. IgG-APS induced higher TF activity in carotid artery homogenates of LPS+/+ mice than in LPS-/- mice. The prevalence of Asp299Gly and Thr399Ile tlr4 polymorphisms was significantly lower than in controls. Conclusions: These findings in LPS-/- mice and the reduction in the "protective" polymorphism in patients with APS with thrombosis suggest that TLR-4 is involved in the interaction of aPL with endothelial cells in vivo.

Original languageEnglish (US)
Pages (from-to)1327-1333
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume66
Issue number10
DOIs
StatePublished - Oct 2007

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Toll-Like Receptors
Lipopolysaccharides
Antiphospholipid Syndrome
Thrombosis
Endothelial cells
Polymorphism
Immunoglobulin G
Endothelial Cells
Toll-Like Receptor 4
Thromboplastin
Systemic Lupus Erythematosus
Microcirculation
Abdominal Muscles
Serum
Carotid Arteries
Venous Thrombosis
Muscle
Leukocytes
Genes
Chemical activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pierangeli, S. S., Vega-Ostertag, M. E., Raschi, E., Liu, X., Romay-Penabad, Z., De Micheli, V., ... Meroni, P. L. (2007). Toll-like receptor and antiphospholipid mediated thrombosis: In vivo studies. Annals of the Rheumatic Diseases, 66(10), 1327-1333. https://doi.org/10.1136/ard.2006.065037

Toll-like receptor and antiphospholipid mediated thrombosis : In vivo studies. / Pierangeli, Silvia S.; Vega-Ostertag, Mariano E.; Raschi, Elena; Liu, Xiaowei; Romay-Penabad, Zurina; De Micheli, Valeria; Galli, Monica; Moia, Marco; Tincani, Angela; Borghi, Maria Orietta; Nguyen-Oghalai, Tracy; Meroni, Pier Luigi.

In: Annals of the Rheumatic Diseases, Vol. 66, No. 10, 10.2007, p. 1327-1333.

Research output: Contribution to journalArticle

Pierangeli, SS, Vega-Ostertag, ME, Raschi, E, Liu, X, Romay-Penabad, Z, De Micheli, V, Galli, M, Moia, M, Tincani, A, Borghi, MO, Nguyen-Oghalai, T & Meroni, PL 2007, 'Toll-like receptor and antiphospholipid mediated thrombosis: In vivo studies', Annals of the Rheumatic Diseases, vol. 66, no. 10, pp. 1327-1333. https://doi.org/10.1136/ard.2006.065037
Pierangeli SS, Vega-Ostertag ME, Raschi E, Liu X, Romay-Penabad Z, De Micheli V et al. Toll-like receptor and antiphospholipid mediated thrombosis: In vivo studies. Annals of the Rheumatic Diseases. 2007 Oct;66(10):1327-1333. https://doi.org/10.1136/ard.2006.065037
Pierangeli, Silvia S. ; Vega-Ostertag, Mariano E. ; Raschi, Elena ; Liu, Xiaowei ; Romay-Penabad, Zurina ; De Micheli, Valeria ; Galli, Monica ; Moia, Marco ; Tincani, Angela ; Borghi, Maria Orietta ; Nguyen-Oghalai, Tracy ; Meroni, Pier Luigi. / Toll-like receptor and antiphospholipid mediated thrombosis : In vivo studies. In: Annals of the Rheumatic Diseases. 2007 ; Vol. 66, No. 10. pp. 1327-1333.
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AU - Liu, Xiaowei

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AU - De Micheli, Valeria

AU - Galli, Monica

AU - Moia, Marco

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