Premium
Stimulation of P2X receptors enhances lipooligosaccharide‐mediated apoptosis of endothelial cells
Author(s) -
Sylte Matt J.,
Kuckleburg Chris J.,
Inzana Thomas J.,
Bertics Paul J.,
Czuprynski Charles J.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1004597
Subject(s) - purinergic receptor , biology , microbiology and biotechnology , apoptosis , apyrase , receptor , purinergic signalling , p2 receptor , endothelial stem cell , adenosine triphosphate , p2y receptor , stimulation , biochemistry , adenosine receptor , endocrinology , agonist , in vitro
Exposure of endothelial cells to lipid A‐containing molecules, such as lipopolysaccharide (LPS) or lipooligosaccharide (LOS), causes the release of purinergic compounds [e.g., adenosine 5′‐triphosphate (ATP)] and can lead to apoptosis. The P2X family of purinergic receptors (e.g., P2X 7 ) has been reported to modulate LPS signaling events and to participate in apoptosis. We investigated the role that P2X receptors play in the apoptosis that follows exposure of bovine endothelial cells to Haemophilus somnus LOS. Addition of P2X inhibitors, such as periodate‐oxidized ATP (oATP) or pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulfonic acid tetrasodium, significantly reduced LOS‐induced apoptosis. Incubation of endothelial cells with apyrase, which degrades ATP, diminished LOS‐induced apoptosis of endothelial cells. Concomitant addition of P2X agonists [e.g., 2′,3′‐(4‐benzoyl)‐benzoyl ATP or ATP] to LOS‐treated endothelial cells significantly enhanced caspase‐3 activation. The P2X antagonist oATP significantly blocked caspase‐8 but not caspase‐9 activation in LOS‐treated endothelial cells. Together, these data indicate that stimulation of P2X receptors enhances LOS‐induced apoptosis of endothelial cells, possibly as a result of endogenous release of ATP, which results in caspase‐8 activation.