Streptococcal pyrogenic exotoxin B-induced apoptosis in A549 cells is mediated through alpha(v)beta(3) integrin and

Wan-Hua Tsai1, Chia-Wen Chang, Yee-Shin Lin

  • 1Institute of Medical Sciences, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.

Infection and Immunity
|January 30, 2008
PubMed

Insights

Streptococcal pyrogenic exotoxin B (SPE B) induces apoptosis via alpha(v)beta(3) integrin and Fas receptors. The RGD motif is critical for alpha(v)beta(3) binding, while Fas mediates apoptosis independently of this motif.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Previous studies indicated streptococcal pyrogenic exotoxin (SPE) B triggers apoptosis through a receptor-mediated pathway.
  • Understanding the specific receptors involved is crucial for elucidating SPE B's pathogenic mechanisms.

Purpose of the Study:

  • To identify the specific cell surface receptors responsible for SPE B-induced apoptosis.
  • To investigate the roles of the RGD motif and identified receptors in the apoptotic process.

Main Methods:

  • Utilized binding assays (fluorescein isothiocyanate-SPE B) and immunoprecipitation to confirm interactions between SPE B, alpha(v)beta(3) integrin, and Fas.
  • Employed blocking antibodies against alpha(v)beta(3) and Fas to assess their impact on SPE B-induced apoptosis.
  • Investigated the effect of SPE B on cell surface receptor levels and utilized proteasome inhibitors to explore downstream mechanisms.

Main Results:

  • Identified alpha(v)beta(3) integrin and Fas as key receptors for SPE B-induced apoptosis.
  • Demonstrated that the RGD motif in SPE B is critical for alpha(v)beta(3) binding and subsequent apoptosis.
  • Showed that Fas mediates apoptosis independently of the RGD motif, and both receptors act synergistically.
  • Observed SPE B-induced downregulation of alpha(v)beta(3) via the ubiquitin-proteasome system.

Conclusions:

  • SPE B induces apoptosis through a synergistic interaction with alpha(v)beta(3) integrin and Fas.
  • The RGD motif is essential for alpha(v)beta(3) engagement, while Fas contributes to apoptosis through an RGD-independent pathway.
  • SPE B triggers endocytosis of alpha(v)beta(3) via the ubiquitin-proteasome pathway, contributing to the apoptotic cascade.

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