Stimulation of P2X receptors enhances lipooligosaccharide-mediated apoptosis of endothelial cells

Abstract

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.

ATP release by infected bovine monocytes increases the intracellular survival of Mycobacterium avium subsp. paratuberculosis

“…These observations are similar to a previous report that murine macrophages constitutively release nM concentrations of ATP, that was not enhanced by addition of bacterial endotoxin (LPS) [14]. However, other investigators reported that LPS enhanced release of ATP from bovine endothelial cells [15]. It has been reported that thrombin, bradykinin, ADP, and oxidative stress increase ATP release from various cells [16] and [17].…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…It has been suggested that ATP, via P2Y 11 receptors, impairs endothelial cells proliferation by inducing cell cycle arrest and sensitizing the cells to cisplatin-induced death (Xiao et al, 2011). There is evidence that stimulation of P2X 7 receptors enhances apoptosis of endothelial cells mediated by lipooligosaccharide, which causes release of ATP (Sylte et al, 2005).…”

“…Expression levels of P2X 4 were significantly higher in endothelium of the human saphenous vein than in the radial and internal mammary arteries, and given that P2X 4 modulates vascular contractility and is upregulated in situations involving intima proliferation, it was suggested that vein grafts used in coronary bypass surgery are more susceptible to developing atherosclerosis (Ray et al, 2002). Stimulation of P2X 7 receptors on bovine pulmonary artery endothelial cells enhances lipopolysaccharide (LPS)-induced apoptosis via caspase-8 activation (Sylte et al, 2005).…”

Characterization and Comparison of Biofilm Development by Pathogenic and Commensal Isolates of Histophilus somni

“…In addition to pneumonia (2,13,21), H. somni can cause meningoencephalitis, myocarditis, arthritis, septicemia, and other systemic infections (7,22). H. somni expresses a wide array of virulence factors, including phase variation of lipooligosaccharide epitopes (20,24,25,52), decoration of lipooligosaccharide with sialic acid and phosphorylcholine (20,24,43), expression of high-molecular-weight immunoglobulin-binding proteins (5,6,51), intracellular survival in professional phagocytes (8,33), and induction of apoptosis (46,47). However, urogenital strains of H. somni lack many of these virulence factors and are incapable or less capable of causing disease than isolates from normally sterile sites (43).…”