Endothelial P2X7 receptors’ expression is reduced by schistosomiasis

Abstract

Endothelial cells control vascular tone, permeability and leukocyte transmigration and are modulated by pro-inflammatory mediators. Schistosomiasis is an intravascular disease associated with inflammation, therefore altering endothelial cells' phenotype. Purinergic P2X7 receptors (P2X7R) play an important role in inflammation; however, the impact of the disease upon endothelial P2X7R function or expression has not been explored. Using ethidium bromide uptake to investigate P2X7R function, we observed that the effects of ATP (3 mM) and the P2X7R agonist 3′-O-(4-benzoyl)-ATP (BzATP) were smaller in mesenteric endothelial cells from the Schistosoma mansoni-infected group than in the control group. In the control group, BzATP induced endothelial nitric oxide production, which was blocked by the P2X7R antagonists KN-62 and A740003. However, in the infected group, we observed a reduced effect of BzATP and no effect of both P2X7R antagonists, suggesting a downregulation of endothelial P2X7R in schistosomiasis. We observed similar results in both infected and P2X7R −/− groups, which were also comparable to data obtained with KN-62-or A740004-treated control cells. Data from Western blot and immunocytochemistry assays confirmed the reduced expression of P2X7R in the infected group. In conclusion, our data show a downregulation of P2X7R in schistosomiasis infection, which likely limits the infection-related endothelial damage.

The role of p2x7 receptor in infectious inflammatory diseases and the influence of ectonucleotidases

“…[55] In accordance with this, recent data also showed a downregulation of P2X7 receptor in schistosomiasis infection, an intravascular disease associated with inflammation, which likely limits the infection-related endothelial damage. [56] Using both in vitro and in vivo models, colchicine has been documented to block the pro-inflammatory signaling downstream of P2X7 receptor activation. It was suggested that the dye uptake associated with the activation of P2X7 receptors is distinct from the P2X7 receptor ion channel and could be a therapeutic target for the treatment of chronic inflammation.…”

Altered expression of P2Y2 and P2X7 purinergic receptors in the isolated rat heart mediates ischemia–reperfusion injury

“…Interestingly, the hearts treated with Brilliant Blue before ischemia showed increased coronary vascular resistance after ischemia. P2X7 receptors are expressed in blood vessel cells [17,22,24,25] therefore they might have a protective preconditioning effect circumscribed to the coronary vascular wall, although its effect on the myocardial cells would be mainly detrimental during reperfusion. It has been described that endothelial P2X7 receptors may induce release of nitric oxide [8,22], which is involved in preconditioning of the vascular ischemia-reperfusion injury [16].…”

Purinergic signaling in schistosomal infection

“…However, excessive P2X 7 receptor activation may lead to apoptosis [99] . Mesenteric endothelial cells from S. mansoni -infected mice exhibited a reduced Ca 2+ influx and ethidium bromide uptake in response to the agonist BzATP [113] . We found that the downregulation of endothelial P2X 7 receptor signaling was related to a reduced protein expression, which also reduced NO production in response to ATP or BzATP.…”

“…Endothelial cells from different vascular beds express several subtypes of purinergic P2Y receptors, including P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 and P2Y 11 receptors [73] , [111] , [112] . Moreover, P2X 4 and P2X 7 receptors [73] , [113] , [114] and NTPDases 1, 2 and 3 are also expressed [85] , [115] .…”

“…Vascular P2X 7 receptors activation induces endothelium-dependent vasodilation [116] and constitutive NO production in cultured endothelial cells [113] . However, excessive P2X 7 receptor activation may lead to apoptosis [99] .…”