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.
Highlights
Schistosoma mansoni causes an intravascular parasitic disease characterized by chronic, systemic inflammation
In order to discriminate whether the absence of ATP- and A23187-induced production of Nitric oxide (NO) in the infected group was due to a reduced activity or expression of the enzyme, we evaluated the expressions of endothelial NO synthase (eNOS) and of caveolin-1, a known inhibitor of eNOS through proteinprotein interaction
The present study provides evidence supported by in vivo and in vitro assays that schistosomiasis increases endothelial cell-leukocyte interaction and vascular permeability
Summary
Schistosoma mansoni causes an intravascular parasitic disease characterized by chronic, systemic inflammation. Endothelial cells are important to vascular homeostasis since they regulate inflammatory events, such as vascular permeability, leukocyte rolling and adhesion to endothelial cell within microcirculation [7,8,9,10]. In schistosomiasis there is an increase in the plasma concentration of soluble intercellular adhesion molecule (ICAM), a classical marker of endothelial activation in inflammation, which correlates to the severity of the disease [12]. Another characteristic of endothelial cells is that some phenotypic changes primed in vivo, such as the expression of adhesion molecules for instance, are kept in vitro [13,14]. We evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro
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