The overall goal of this research is to describe the mechanisms involved in the migration of schistosome eggs from the venule of the intestinal wall into the lumen of the intestine. The specific goal of this project is to determine the mechanisms involved in egg adhesion to and passage through venular endothelium. This will be accomplished by using an in vitro model, confluent monolayers of human umbilical cord vein and rabbit portal vein endothelial cells. Promising preliminary studies indicate that the model will be useful for revealing the basic features of this process. Schistosoma mansoni and S. japonicum eggs will be used in an Egg Adhesion Assay. (% of eggs adhering to endothelial monolayer after specific contact time). The nature of the primary recognition factors will be studied after enzymatic removal of specific glycoproteins, inhibition or blocking with lectins and/or anti-egg antibodies. Inhibition of inflammation and endogenous prostaglandin synthesis will also be accomplished with appropriate agents to determine the involvement of these mechanisms. The possibility of egg or worm induced endothelial proliferation will be investigated using autoradiographic methods. Scanning electron microscopy will be used to monitor normal and interrupted egg interaction with the cell monolayers. Understanding how and which eggs do not microembolize to the liver may or may not allow manipulation of this aspect of schistosome infection but may well help identify those individuals at risk of most severe disease.
|File, S (1995) Interaction of schistosome eggs with vascular endothelium. J Parasitol 81:234-8|
|Cooper, L A; Lewis, F A; File-Emperador, S (1989) Re-establishing a life cycle of Schistosoma mansoni from cryopreserved larvae. J Parasitol 75:353-6|