Inhibition of the Complement Membrane Attack Complex by Schistosoma mansoni Paramyosin

Jiusheng Deng, Daniel Gold, Philip T Loverde, Zvi Fishelson

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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 Zn2+-induced C9 polymerization and poly-C9 deposition onto rabbit erythrocytes (ER). In addition, paramyosin inhibited lysis of ER 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.

Original languageEnglish (US)
Pages (from-to)6402-6410
Number of pages9
JournalInfection and Immunity
Volume71
Issue number11
DOIs
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

Complement Membrane Attack Complex
Tropomyosin
Schistosoma mansoni
Erythrocytes
Complement Inactivating Agents
Complement C8
Anti-Idiotypic Antibodies
Complement C9
Rabbits
Trematoda
Muscle Proteins
Schistosomiasis
Thrombin
Polymerization
Trypsin
Fluorescent Antibody Technique
Larva
Immune Sera
Mass Spectrometry
Sheep

ASJC Scopus subject areas

  • Immunology

Cite this

Inhibition of the Complement Membrane Attack Complex by Schistosoma mansoni Paramyosin. / Deng, Jiusheng; Gold, Daniel; Loverde, Philip T; Fishelson, Zvi.

In: Infection and Immunity, Vol. 71, No. 11, 11.2003, p. 6402-6410.

Research output: Contribution to journalArticle

Deng, Jiusheng ; Gold, Daniel ; Loverde, Philip T ; Fishelson, Zvi. / Inhibition of the Complement Membrane Attack Complex by Schistosoma mansoni Paramyosin. In: Infection and Immunity. 2003 ; Vol. 71, No. 11. pp. 6402-6410.
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