Schistosoma mansoni: praziquantel-induced tegumental lesion exposes actin of surface spines and allows binding of actin depolymerizing factor, gelsolin.
Praziquantel is widely used for treatment of schistosomiasis. Elimination of intravascular worms involves a combination of drug-induced changes at the worm surface and a host immune response against exposed parasite components. Loss of spines is a typical feature of schistosomes obtained from praziquantel-treated infected animals. The mechanism for this is unknown. We have considered the possibility that praziquantel treatment involves exposure of surface spines consisting of 'paracrystalline' actin and a subsequent host response against actin through mechanisms established in the host independently from schistosomal infection. Drug-induced exposure of actin was demonstrated by fluorescence microscopy using anti-actin antibodies and phallacidin, an actin-binding mushroom toxin. Actin spines remained intact at the schistosome surface after in vitro exposure, but spine morphology was lost after in vivo exposure to praziquantel. Disintegration of spines in vivo was associated with binding of host antibodies. In vitro spine destruction could be seen in the presence of normal human serum. The effect was linked to calcium-dependent binding of actin depolymerizing factor, gelsolin.
Linder
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E
Department of Parasitology, National Bacteriological Laboratory, Stockholm, Sweden.
Thors
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C
D000199:Actins / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000097:blood / Q000378:metabolism*; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D005629:Frozen Sections; D018260:Gelsolin; D006801:Humans; D008840:Microfilament Proteins / Q000097:blood / Q000378:metabolism*; D008854:Microscopy, Electron; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D000199:Actins; D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D018260:Gelsolin; D008840:Microfilament Proteins; D011223:Praziquantel