β2-glycoprotein I and oxidative inflammation in early atherogenesis: A progression from innate to adaptive immunity?

Eiji Matsuura, Luis R. Lopez, Yehuda Shoenfeld, Paul R.J. Ames

Research output: Contribution to journalReview article

36 Citations (Scopus)

Abstract

The innate immune system represents the first line of host defense against a wide variety of pathogens and endogenous danger signals. It relies on trans-membrane signaling and cytoplasmic receptors (danger sensors) to trigger early inflammatory responses. As with the adaptive immunity, an innate immune response can cause tissue injury, chronic inflammation and disease. Nucleotide-binding leucine-rich proteins (NLRs) are a family of cytoplasmic receptors for endogenous danger signals. Inflammasomes are multi-molecular complexes of pyrin-containing NLRs (NLRPs) that regulate pro-inflammatory caspases and interleukin 1 cytokines in response to various stimuli. Cholesterol crystals and oxidation-specific epitopes (oxLDL, ROS) are some of the endogenous signals capable of activating NLRP inflammasomes. Thus, an inflammasome-induced IL-1β dysregulation may represent an early atherogenic mechanism that initiates atherosclerosis. The plasma protein, β2-glycoprotein I (β2GPI), complexed to anionic phospholipids is the main antigenic target for antiphospholipid antibodies. In addition to anticoagulant properties, circulating β2GPI has more pleiotropic functions affecting fibrinolysis, angiogenesis, apoptosis and atherogenesis. OxLDL interacts with β2GPI to form oxLDL/β2GPI pro-atherogenic complexes in both autoimmune-mediated and non-autoimmune atherothrombotic diseases. Due to its interaction with oxLDL, the contribution and implication of β2GPI in early atherogenesis via the innate (inflammasome/IL-1) system are hypothesized.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalAutoimmunity Reviews
Volume12
Issue number2
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Atherosclerosis
  • Immune system
  • Inflammation
  • Oxidative stress
  • β2-Glycoprotein I (β2GPI)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'β2-glycoprotein I and oxidative inflammation in early atherogenesis: A progression from innate to adaptive immunity?'. Together they form a unique fingerprint.

  • Cite this