Portal veins of mice infected with Schistosoma mansoni exhibit an increased reactivity to 5-hydroxytryptamine

Abstract

Key words: portal vein -Schistosoma mansoni -endothelium -5-hydroxytryptamineSchistosoma mansoni is mainly located in the mesenteric vessels where the female worms lay hundreds of eggs daily during years (Webbe 1981), leading to a granulomatous response. The anatomical and physiological changes that occur in the portal vasculature during a chronic severe infection accompany the portal hypertension as a consequence of the periportal fibrosis (Bosch et al. 1992, File 1995, Moreno et al. 1996. Since the male worm can fix to the endothelium via its ventral sucker, a direct effect (that means independent of an inflammatory response to eggs) on vein endothelium could also be responsible for an alteration of vascular reactivity. To investigate this possibility we used mice infected unisexually with male worms for studying the contractile response of portal vein to 5-hydroxytryptamine (5-HT), an endogenous agonist that is already known to be involved in the maintenance of mesenteric venous tone. A possible alteration of the endothelial larginine/nitric oxide pathway (Moncada et al. 1991, Salomone et al. 1996 was also investigated. MATERIALS AND METHODSInfection of mice -Male cercariae of S. mansoni (BH strain) were obtained from snails (Biomphalaria glabrata) previously infected with a single male miracidium. Newborn Swiss white mice (3-5 days) were then infected percutaneously with approximately 150 cercariae.In vitro experiment -The animals were anesthetized with ether and killed by cervical dislocation about 75 days after the infection. The portal vein was carefully removed, freed of connective tissue and worms removed from the veins by flushing physiological solution in the lumen. The same treatment was applied to the veins isolated from non-infected mice. About 5 mm of tissue was set up longitudinally in a bath filled with physiological solution (NaCl 122 mM, KCl 5 mM, NaHCO 3 15 mM, glucose 11.5 mM, MgCl 2 1.2 mM, CaCl 2 1.25 mM and KH 2 PO 4 1.2 mM) bubbled with a mixture of 95% O 2 and 5% CO 2 at 37 o C. The tension generated was recorded using an isometric transducer connected to a data acquisition system and further quantitated by integration of the tension-time curve over a period of 1-3 min. The integrated tension (expressed in mN.s) was corrected to represent the mean integrated tension for a period of 1 sec. The drug-induced tension referred to the difference in the integrated contractile activity measured immediately before and during the application of the drug. The tissue was equilibrated

Interference with the Host Haemostatic System by Schistosomes

“…Schistosomes are potential activators of the extrinsic pathway due to the induction of turbulence and endothelial damage and/or alteration of endothelial function induced by the adult parasite and/or the eggs [8], [9], [16]. Furthermore, elevated levels of tumor necrosis factor alpha (TNF-α) are present in schistosomiasis patients, and high TNF-α levels are known to induce TF expression on endothelial cells in vitro [50], [54].…”

“…On average, adult schistosomes reside in their host's bloodstream for three to five years, but their individual lifespan can be as long as 30 years [7]. Schistosomes can be expected to activate coagulation according to Virchow's triad by inducing stasis and alterations in endothelial function [8], [9]. The adult schistosome pair disturbs blood flow due to the large size of the worm pair: 1 cm long with a diameter of 1 mm (Figure 1).…”

“…Turbulence and changes in shear stress, induced by the presence of the adult schistosome pair in the blood vessel, could potentially activate platelets and blood coagulation [4], [11]. In addition, although there is no direct evidence of endothelial damage caused by the presence of the adult worm pair in the vein, several studies suggest that schistosomes disturb endothelial cell function, and it has been suggested that the presence of the adult worm in the vein induces endothelial damage [9], [19]–[21]. In murine schistosomiasis, the expression of endothelial NO synthase as well as the production of NO are decreased, which indicates endothelial dysfunction [9], [19], [21].…”

“…In addition, although there is no direct evidence of endothelial damage caused by the presence of the adult worm pair in the vein, several studies suggest that schistosomes disturb endothelial cell function, and it has been suggested that the presence of the adult worm in the vein induces endothelial damage [9], [19]–[21]. In murine schistosomiasis, the expression of endothelial NO synthase as well as the production of NO are decreased, which indicates endothelial dysfunction [9], [19], [21]. Furthermore, plasma soluble intercellular adhesion molecule-1 is increased in hepatosplenic schistosomiasis patients, which indicates endothelial activation and inflammation [22].…”

Proteomic identification of endothelial cell surface proteins isolated from the hepatic portal vein of mice infected with Schistosoma bovis

“…Some in vitro studies have shown that the products secreted by the schistosomula of S. mansoni limit inflammation through the induction of IL-6 and down regulation of the adhesion molecules E-selectin and VCAM-1 in endothelial cells, thereby avoiding the immune/inflammatory response during their transit through the lungs [13][14][15]. It has also been found that the adult worms of the same species exert a regulatory effect on the release of nitric oxide [16]. More recently, studies performed with endothelial cell cultures from mesenteric microvasculature have demonstrated that schistosomes increase vascular permeability and endothelial cellleukocyte interactions, and that these effects are partially caused by a decrease in the expression of endothelial NO synthase (eNOS) [17].…”