Shortly after infection of the human host, schistosomula of the parasite Schistosoma mansoni produce a double membrane which completely envelops the organism. These surface membranes, known as the tegumental membranes, serve as the interface between host and parasite and may protect the parasite from the host's immune system. Although the outermost of these membranes, the outer tegumental membrane, is thought to be composed predominantly of lipid, data concerning the composition, synthesis and function of the tegumental membranes are incomplete. Further, studies have shown that praziquantel, an important drug for the treatment of schistosomiasis, alters the properties of lipid bilayers and that lipids can affect the humoral immune response to schistosomula. Thus, knowledge of the parasite's lipid composition and metabolism, in general, and of the tegumental membranes, in particular, is important for understanding the host/parasite relationship. In initial studies, labeled lipid released from cultured schistosomula has been examined as an indication of the lipid composition of the outer of the outer tegumental membrane. High levels of lysophosphatidylcholine (LPC) have been found in these experiments and the presence of this lipid could explain a number of phenomena that occur in human cells adherent to cultured schistosomula. THe primary goal of this work is a detailed lipid biochemical analysis of this parasite with particular emphasis on the lipid composition and metabolism of the tegumental membranes. The major lipid classes from the intact parasites and isolated tegumental membranes will be separated and identified. Lipid metabolism will be followed in both using radioactive precursors and it will be determined, in vitro, which lipid components of serum affect the worm's viability. Lipids on the surface of the parasite will be further characterized by using surface labeling with 125I. The phospholipase responsible for the generation of LPC will be isolated from the worm and characterized. Phospholipase inhibitors or other drugs known to inhibit lipid synthesis in other systems will be tested for their ability to alter the lipid metabolism of adults or schistosomula. Subsequently, parasites whose lipid composition has been altered either by drugs, or by incubation with lipid precursor analogs or lipid vesicles will be tested to determine if such treatment influences antibody or complement binding, or host cell interaction with the surface of the worm. Ultimately, these studies could lead to a model of how the lipid composition of the tegumental membranes influences the parasite's interaction with the host.
