Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils

Journal Article · Fri Jan 01 04:00:00 EST 2010 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.10.141· OSTI ID:22199950

Binet, Francois; Chiasson, Sonia ^[1]; Girard, Denis ^[1]

---

1. Laboratoire de recherche en inflammation et physiologie des granulocytes, Universite du Quebec, INRS-Institut Armand-Frappier, Laval, QC (Canada)

Apoptosis can result from activation of three major pathways: the extrinsic, the intrinsic, and the most recently identified endoplasmic reticulum (ER) stress-mediated pathway. While the two former pathways are known to be operational in human polymorphonuclear neutrophils (PMNs), the existence of the ER stress-mediated pathway, generally involving caspase-4, has never been reported in these cells. Recently, we have documented that arsenic trioxide (ATO) induced apoptosis in human PMNs by a mechanism that needs to be further investigated. In this study, using immunofluorescence and electron microscopy, we present evidence of ER alterations in PMNs activated by the ER stress inducer arsenic trioxide (ATO). Several key players of the unfolded protein response, including GRP78, GADD153, ATF6, XBP1 and eIF2{alpha} are expressed and activated in PMNs treated with ATO or other ER stress inducers. Although caspase-4 is expressed and activated in neutrophils, treatment with a caspase-4 inhibitor did not attenuate the pro-apoptotic effect of ATO at a concentration that reverses caspase-4 processing and activation. Our results demonstrate for the first time that the ER stress-mediated apoptotic pathway operates in human neutrophils.

• OSTI ID: 22199950
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 391; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
ARSENIC
BIOLOGICAL STRESS
CONCENTRATION RATIO
ECOLOGICAL CONCENTRATION
ELECTRON MICROSCOPY
ENDOPLASMIC RETICULUM
HUMAN POPULATIONS
NEUTROPHILS
PROTEINS