This proposal has three major goals, all of which center on the surface of the human parasite Schistsosoma mansoni. First, the cercarial glycocalyx will be analyzed biochemically and immunologically in order to test its suitability as a candidate for a vaccine. The glycocalyx is highly antigenic, reacts with a protective mnonoclonal antibody, and is a mildly acidic glycoprotein that is over half carbohydrate. The glycocalyx will be purified, analyzed, fragmented and both the intact molecule and fragments will be tested for their ability to protect mice from schistosome infections. A second goal is to determine how the parasite protects itself from attack by cells of the host's immune system. In particular, the parasite lyses human granulocytes and acquires host membrane components. The mechanism of lysis will be explored with fluorescence photobleaching recovery techniques and the mechanism of host antigen acquisition with electron microscopic immunocytoochemnistry and freeze fracture. If these mechanism can be determined, the phenomena may be inhibited therapeutically with a resulting decrease in infection. Finally, since the surface of the parasite is syncytium covered by two lipid bilayers, the outer of which appears to contain very little protein, the lipid composition and biosynthesis of the surface will be examined by radiolabeling and HPLC. Many properties of the parasite surface can be attributed potentially to its lipids. Knowledge of the lipid makeup and turnover of the surface membranes may lead to the ability to produce biochemical alterations in these membranes which make the worm susceptible to immune killing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI023083-04
Application #
3565488
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-07-01
Project End
1990-03-31
Budget Start
1988-12-01
Budget End
1990-03-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Khoo, K H; Chatterjee, D; Caulfield, J P et al. (1997) Structural characterization of glycophingolipids from the eggs of Schistosoma mansoni and Schistosoma japonicum. Glycobiology 7:653-61
Khoo, K H; Chatterjee, D; Caulfield, J P et al. (1997) Structural mapping of the glycans from the egg glycoproteins of Schistosoma mansoni and Schistosoma japonicum: identification of novel core structures and terminal sequences. Glycobiology 7:663-77
Jiang, J; Skelly, P J; Shoemaker, C B et al. (1996) Schistosoma mansoni: the glucose transport protein SGTP4 is present in tegumental multilamellar bodies, discoid bodies, and the surface lipid bilayers. Exp Parasitol 82:201-10
Jiang, J; Caulfield, J P; Markovics, A et al. (1996) Schistosoma mansoni: localization of the SmIMP25 protein in the subtegumental extracellular matrix of schistosomula. Exp Parasitol 82:218-21
Khoo, K H; Sarda, S; Xu, X et al. (1995) A unique multifucosylated -3GalNAc beta 1-->4GlcNAc beta 1-->3Gal alpha 1- motif constitutes the repeating unit of the complex O-glycans derived from the cercarial glycocalyx of Schistosoma mansoni. J Biol Chem 270:17114-23
Zhong, C; Skelly, P J; Leaffer, D et al. (1995) Immunolocalization of a Schistosoma mansoni facilitated diffusion glucose transporter to the basal, but not the apical, membranes of the surface syncytium. Parasitology 110 ( Pt 4):383-94
Cohn, R G; Williams, M; Sher, A et al. (1995) Schistosoma mansoni: characterization of an Fc epsilon R+ population of granule-containing splenocytes isolated from infected mice. Exp Parasitol 80:339-41
Xu, X; Stack, R J; Rao, N et al. (1994) Schistosoma mansoni: fractionation and characterization of the glycocalyx and glycogen-like material from cercariae. Exp Parasitol 79:399-409
Rein, M S; Barbieri, R L; Welch, W et al. (1993) The concentrations of collagen-associated amino acids are higher in GnRH agonist-treated uterine myomas. Obstet Gynecol 82:901-5
Xu, X; Remold, H G; Caulfield, J P (1993) Potential role for scavenger receptors of human monocytes in the killing of Schistosoma mansoni. Am J Pathol 142:685-9

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