Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin.
Larvae and adults of the parasitic blood fluke Schistosoma mansoni are resistant to killing by human complement. An earlier search by Parizade et al. for a schistosome complement inhibitor identified a 94-kDa surface protein which was named SCIP-1 (M. Parizade, R. Arnon, P. J. Lachmann, and Z. Fishelson, J. Exp. Med. 179:1625-1636, 1994). Following partial purification and analysis by mass spectrometry, we have determined SCIP-1 to be a surface-exposed form of the muscle protein paramyosin. As shown by immunofluorescence, anti-paramyosin antibodies label the surface of live schistosomula and adult worms. Like SCIP-1, purified native paramyosin reacts with a polyclonal rabbit anti-human CD59 antiserum, as shown by Western blot analysis. Also, the human complement components C8 and C9 bind to recombinant and native paramyosin. Analysis of paramyosin binding to fragments of C9 generated by thrombin or trypsin has demonstrated that paramyosin binds to C9 at a position located between Gly245 and Arg391. Paramyosin inhibited Zn(2+)-induced C9 polymerization and poly-C9 deposition onto rabbit erythrocytes (E(R)). In addition, paramyosin inhibited lysis of E(R) and of sensitized sheep erythrocytes by human complement. Finally, anti-paramyosin antibodies enhanced in vitro killing of schistosomula by normal and C4-depleted human complement. Taken together, these findings suggest that an exogenous form of S. mansoni paramyosin inhibits activation of the terminal pathway of complement and thus has an important immunomodulatory role in schistosomiasis.
Departments of Human Microbiology. Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Jiusheng
J
Deng
Daniel
D
Gold
Philip T
PT
LoVerde
Zvi
Z
Fishelson
D000818:Animals; D018957:CD59 Antigens / Q000502:physiology; D003185:Complement C8 / Q000378:metabolism; D003186:Complement C9 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors*; D005455:Fluorescent Antibody Technique; D015801:Helminth Proteins / Q000502:physiology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D012550:Schistosoma mansoni / Q000276:immunology*; D014335:Tropomyosin / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
D018957:CD59 Antigens; D003185:Complement C8; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D015801:Helminth Proteins; D014335:Tropomyosin; D015032:Zinc