Published ahead of print on April 28, 2005, doi:10.1165/rcmb.2005-0056OC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 2, August 2005, 169-177 A more recent version of this article appeared on August 1, 2005
Submitted on February 8, 2005 Diverse Effects of Eosinophil Cationic Granule Proteins on IMR-32 Nerve Cell Signalling and SurvivalRoss K Morgan1,1 Department of Medicine, Beaumont Hospital, Dublin, Ireland, 2 Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom, 3 Departments of Dermatology and Medicine, University of Utah, Utah, USA * To whom correspondence should be addressed. E-mail: rcostello{at}rcsi.ie.
Activated eosinophils release potentially toxic cationic granular proteins, including the major basic proteins (MBP) and eosinophil-derived neurotoxin (EDN). However, in inflammatory conditions including asthma and inflammatory bowel disease, localisation of eosinophils to nerves is associated with nerve plasticity, specifically remodelling. In previous in vitro studies, we have shown that eosinophil adhesion to IMR-32 nerve cells, via nerve cell ICAM-1, results in an adhesion-dependent release of granule proteins. We hypothesised that released eosinophil granule proteins may affect nerve cell signalling and survival leading to nerve cell remodelling. Culture in serum-deprived media induced apoptosis in IMR-32 cells that was dose-dependently abolished by inclusion of MBP1 but not by EDN. Both MBP1 and EDN induced phosphorylation of Akt, but with divergent time courses and intensities, and survival was independent of Akt. MBP1 induced activation of neural NF-
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B, from 10 min to 12 h, declining by 24 h, whereas EDN induced a short-lived activation of NF-
