Mechanisms of evasion of Schistosoma mansoni schistosomula to the lethal activity of complement.
Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE) whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF), a 70 kDa glycoprotein attached to the membrane of NHuE by a GPI anchor. IgG2a mAb anti-human DAF (IA10) immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre-incubated with NHuE and inhibited their resistance to complement-dependent killing in vitro. Incubation of schistosomula with erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNHE) or SRBC, which are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polypeptide(s) present on the surface of the worm.
Ramalho-Pinto
F J
FJ
Departamento de Bioquímica-Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
Carvalho
E M
EM
Horta
M F
MF
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018958:CD55 Antigens; D002918:Chymotrypsin / Q000494:pharmacology; D003169:Complement Inactivator Proteins / Q000172:deficiency / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology*; D003470:Culture Media / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology; D006168:Guinea Pigs; D015801:Helminth Proteins / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology / Q000469:parasitology; D007814:Larva; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D012550:Schistosoma mansoni / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000469:parasitology; D012756:Sheep; D014357:Trypsin / Q000494:pharmacology
D015703:Antigens, CD; D018958:CD55 Antigens; D003169:Complement Inactivator Proteins; D003470:Culture Media; D015801:Helminth Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; D003165:Complement System Proteins; D002918:Chymotrypsin; D014357:Trypsin