Increased Endothelial Cell-Leukocyte Interaction in Murine Schistosomiasis: Possible Priming of Endothelial Cells by the Disease

Abstract

Background and AimsSchistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro.Methodology and Principal FindingsThe experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF). Nitric oxide (NO) donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS) increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups.Conclusion/SignificanceSchistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially explained by a reduced eNOS expression. In addition, our data show that the disease primes endothelial cells in vivo, which keep the acquired phenotype in culture.

Endothelial P2X7 receptors’ expression is reduced by schistosomiasis

“…Both agonists had no effect when using endothelial cells from P2X7R −/− mice, suggesting that the agonists' effects were related to P2X7 receptor activation. Then, using another experimental protocol, namely NO measurement, we observed that endothelial P2X7 receptor activation with the agonist BzATP induced NO synthesis in an amount similar to that observed with ATP either in murine [15] or rat endothelial cells [40]. Two P2X7 receptor antagonists (KN-62 and A740003) blocked this effect.…”

“…In the course of schistosomiasis, worms, eggs and their soluble antigens, i.e., a complex mixture of proteins, glycoproteins and glycolipids, interact with vascular endothelium [49] and myocytes causing morphological alterations [4,8,34,35,[50][51][52]. Previous data showed that schistosomiasis is associated with a reduction of mesenteric endothelial eNOS expression and ATP-induced NO production [15]. Despite these findings, the influence of schistosomiasis on host endothelial cells physiology and purinergic signalling has not been deeply explored.…”

“…Nitric oxide (NO) is a potent endothelium-derived vasodilator that at physiological concentrations inhibits endothelium-leukocyte adhesion and cytokine-induced cellular migration [12][13][14]. Recently, we showed that schistosomiasis reduces the expression of the constitutive endothelial NO synthase (eNOS) and the related ATPinduced NO production [15].…”

“…mansoni interacts with the mesenteric endothelium, and the associated inflammation alters endothelial cell phenotype [15,34,35]. Additionally, the worms are able to modulate the host purinergic system through the expression of ectonucleotidases [36].…”

The Interaction of Leukocytes and Adhesion Molecules in Mesenteric Microvessel Endothelial Cells after Internal Capsule Hemorrhage

“…The key preliminary step of inflammation and transmigration is concerned with leukocyte–endothelium adhesion. Recent research shows that leukocyte–endothelium adhesion not only induces angiostenosis or blockage, but also is the precondition of tissue damages mediated by neutrophils [24]. It has been demonstrated that fructose can induce leukocytes adherence to the mesenteric venules of the rat via reactive oxygen species generation [23].…”