Selective release of a glycosylphosphatidylinositol-anchored antigen from the surface of Schistosoma mansoni.
We have recently demonstrated that a 200-kDa antigen that serves as a target of antibodies acting in synergy with praziquantel is linked to the surface membrane of Schistosoma mansoni by a glycosylphosphatidylinositol (GPI) anchor. In the present study we have examined the potential role of this GPI anchor in the therapeutic action of praziquantel by monitoring the release of surface antigens from living adult schistosomes cultured in the presence or absence of praziquantel and exogenous phospholipases. Phosphatidylinositol-specific phospholipase C (PIPLC) selectively released the 200-kDa antigen from the surface of adult schistosomes, as determined by immunoprecipitation experiments; none of the other GPI-anchored proteins, including alkaline phosphatase and a 22-kDa protein, were released by this enzyme. Anti-cross-reacting determinant antiserum (anti-CRD), which recognizes an epitope on GPI-anchored proteins only after the anchor has been removed by PIPLC, specifically precipitated the 200-kDa antigen, confirming the cleavage of its anchor. When the worms were exposed to both praziquantel and PIPLC, the amount of 200-kDa cleaved from the worms was increased five-fold. The selective release of this antigen was also detected by indirect immunofluorescent labeling of praziquantel-exposed adult worms cultured in the presence of phospholipases. Taken together these observations suggest that modulation of the phospholipase-mediated release of GPI-anchored antigens by praziquantel may contribute to the therapeutic action of the drug.
Sauma
S Y
SY
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.
Tanaka
T M
TM
Strand
M
M
D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D005260:Female; D006017:Glycolipids / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols; D051379:Mice; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011223:Praziquantel / Q000494:pharmacology; D011233:Precipitin Tests; D012550:Schistosoma mansoni / Q000187:drug effects / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000276:immunology
D000947:Antigens, Helminth; D000954:Antigens, Surface; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D010716:Phosphatidylinositols; D011223:Praziquantel; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase