| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Research Abstract |
We demonstrated that, in Strongyloides venezuelensis infection in mice, adult worms of S.venezuelensis were actively moving in the intestinal mucosa, exiting and re-entering repeatedly, and that the mechanism for S.venezuelensis expulsion is the inhibition by mast cell glycosaminoglycans of re-invasion of adult worms into intestinal epithelium. Intestinal mastocytosis. prevented surgically implanted adult worms from invading into the intestinal mucosa, and mast cell glycosaminoglycans such as chondroitin sulfate A, chondroitin sulfate E,and heparin, also inhibited invasion of adult worms in vivo. Adult S.venezuelensis worms attach to the intestinal epithelial cells upon invasion by orally secreted heparin-binding adhesion substances. Mast cell glycosaminoglycans inhibited binding of secreted adhesion substances to intestinal epithelial cells in a dose-dependent manner, thus blocking attachment and subsequent invasion.
A mouse monoclonal antibody against secreted adhesion substances (286
… More
-3D7, IgG1, κ) revealed that worms continuously secreted the substances during infection, forming tunnel wall around them. Secreted adhesion substances, therefore, might play a major role in intestinal parasitism in S.venezuelensis infection. 286-3D7 inhibited adhesion of adult worms to plastic surface as well as binding of secreted adhesion substances to intestinal epithelial cells. Antibodies thus could be inhibitory to adult worm invasion. Rabbit polyclonal antibodies against secreted adhesion substances recognized 2-3 proteins in soluble adult antigens, including a heparin-binding protein of 42.0 kDa, which was consistently expressed by adult worms during infection. This protein therefore seemed a possible component of heparin-binding adhesion substances.
Direct sequencing of proteins in secreted adhesion substances revealed no apparent homologous proteins even in Caenorhabditis elegans. Molecular cloning of cDNA for these important proteins would bring us further understanding of intestinal nematode biology and a strong tool to induce protective immunity against strongyloidiasis. Less
|
