Mechanism of Siglec-8-induced human eosinophil apoptosis: Role of caspases and mitochondrial injury

Esra Nutku, Sherry A. Hudson, Bruce S. Bochner

Research output: Contribution to journalArticle

Abstract

Sialic acid binding immunoglobulin like lectin (Siglec)-8 crosslinking with specific antibodies causes human eosinophil apoptosis. Mechanisms by which Siglec-8 crosslinking induces apoptosis are not known. Peripheral blood eosinophils were examined for caspase, mitochondria and reactive oxygen species (ROS) involvement after incubating the cells with anti-Siglec-8 crosslinking Abs or control Abs, in the presence or absence of selective inhibitors. Siglec-8 crosslinking induced rapid cleavage of caspase-3, caspase-8, and caspase-9 in eosinophils. Selective caspase-8 and/or caspase-9 inhibitors inhibited this apoptosis. Siglec-8 crosslinking on eosinophils increased dissipation of mitochondrial membrane potential upstream of caspase activation. Rotenone and antimycin, inhibitors of mitochondrial respiratory chain components, completely inhibited apoptosis. Additional experiments with an inhibitor of ROS, diphenyleneiodonium, demonstrated that ROS was also essential for Siglec-8-mediated apoptosis and preceded Siglec-8-mediated mitochondrial dissipation. These experiments show that Siglec-8-induced apoptosis occurs through the sequential production of ROS, followed by induction of mitochondrial injury and caspase cleavage.

Original languageEnglish (US)
Pages (from-to)918-924
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume336
Issue number3
DOIs
StatePublished - Oct 28 2005

Fingerprint

Sialic Acid Binding Immunoglobulin-like Lectins
Caspases
Eosinophils
Apoptosis
Wounds and Injuries
Crosslinking
Reactive Oxygen Species
Caspase 9
Caspase 8
Rotenone
Mitochondria
Caspase Inhibitors
Mitochondrial Membrane Potential
Electron Transport
Caspase 3
Blood
Experiments
Chemical activation

Keywords

  • Apoptosis
  • Caspases
  • Human eosinophils
  • Mitochondria
  • Siglec-8
  • TMRE staining

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Mechanism of Siglec-8-induced human eosinophil apoptosis : Role of caspases and mitochondrial injury. / Nutku, Esra; Hudson, Sherry A.; Bochner, Bruce S.

In: Biochemical and Biophysical Research Communications, Vol. 336, No. 3, 28.10.2005, p. 918-924.

Research output: Contribution to journalArticle

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