Date of Award

1984

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

This study provides information concerning the factors involved in regulating apical bilayer formation and turnover in the human parasite Schistosoma mansoni. The major phospholipid of cercaria, adults and the outer bilayer and plasma membrane of the apical bilayer complex of the adult parasites is phosphatidylcholine. Phosphatidylcholine was synthesized through the incorporation of choline but not through the methylation of phosphatidylethanolamine.;The uptake and incorporation of choline into phosphatidylcholine by adult S. mansoni was examined in the presence of a variety of sera, hormonal and pharmacologic factors. The examination of sera from a number of sources revealed that permissiveness to infection was not a factor in affecting choline incorporation. However, a heat-labile component of serum increased choline incorporation by adult S. mansoni. The purified C3/C4 components of serum were shown to stimulate choline incorporation into phosphatidylcholine by adult S. mansoni but not schistosomula. The addition of 5-hydroxytryptamine to incubation media stimulated choline incorporation by both schistosomula and adults. The C3/C4 complement components stimulated choline incorporation into phosphatidylcholine of the outer bilayer of the apical bilayer complex of adults and 5-hydroxytryptamine stimulated incorporation into the inner bilayer.;Calcium influx into adult S. mansoni was increased in the presence of C3/C4 but not 5-hydroxytryptamine. Efflux of calcium was increased with 5-hydroxytryptamine but not C3/C4. A model for the signal transduction of C3/C4 is presented in which the binding of C3/C4 to the outer bilayer of the apical surface results in an influx of calcium, an increased rate of apical membrane precursor fusion with the surface, a depletion of membrane precursor organelles and finally an increase the synthesis of membrane. The model presented for the action of 5-hydroxytryptamine is through the direct stimulation of membrane phosphatidylcholine synthesis, mediated by a 5-hydroxytryptamine - adenyl cyclase signal mechanism.

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