Time-dependent apoptosis of alveolar macrophages from rats exposed to bleomycin: involvement of tnf receptor 2

Journal of Toxicology and Environmental Health. Part a
H W ZhaoJ Y C Ma

Abstract

Tumor necrosis factor-alpha (TNF-a) is produced by alveolar macrophages (AM) in response to bleomycin (BLM) exposure. This cytokine has been linked to BLM-induced pulmonary inflammation, an early drug effect, and to lung fibrosis, the ultimate toxic effect of BLM. The present study was carried out to study the time dependence of apoptotic signaling pathways and the potential roles of TNF receptors in BLM-induced AM apoptosis. Male Sprague-Dawley rats were exposed to saline or BLM (1 mg/kg) by intratracheal instillation. At 1, 3, or 7 d postexposure, AM were isolated by bronchoalveolar (BAL) lavage and evaluated for apoptosis by ELISA. The release of cytochrome c from mitochrondria, the activation of caspase-3, -8, and -9, the cleavage of nuclear poly(ADP-ribose) polymerase (PARP), and the expression of TNF receptors (TNF-R1/p55 and TNF-R2/p75), TNF-R-associated factor 2 (TRAF2), and cellular inhibitor of apoptosis 1 (c-IAP1) were determined by immunoblotting. The results showed that BLM exposure induced AM apoptosis, with the highest apoptotic effect occurring at 1 d after exposure and gradually decreasing at 3 and 7 d postexposure, but still remaining significantly above the control level. The maximal translocation of cytochro...Continue Reading

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Citations

Jul 14, 2012·Pulmonary Medicine·Fotios DrakopanagiotakisDemosthenes Bouros
Dec 21, 2010·American Journal of Respiratory and Critical Care Medicine·Xin LinJia Guo
May 16, 2013·American Journal of Respiratory Cell and Molecular Biology·Alexander V MisharinHarris Perlman
Apr 22, 2005·Journal of Cellular Biochemistry·R KoslowskiM Kasper
May 2, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Christina KlothElena Lopez-Rodriguez
Dec 3, 2016·Cell Death & Disease·Daniela SiegmundHarald Wajant

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