A Blood Fluke Serine Protease Inhibitor Regulates an Endogenous Larval Elastase*

Background: Schistosoma mansoni skin degradation is mediated by a serine protease, cercarial elastase (SmCE). Results: A parasitic serpin, SmSrpQ, covalently binds to SmCE and is released into the host as the parasite penetrates the skin. Conclusion: SmSrpQ regulates the tissue-degrading activity of SmCE inside the host. Significance: SmSrpQ regulation of SmCE represents an important mechanism by which the parasite balances tissue penetration and host tissue damage. The larvae of Schistosoma mansoni invade their mammalian host by utilizing a serine protease, cercarial elastase (SmCE), to degrade macromolecular proteins in host skin. The catalytic activity of serine and cysteine proteases can be regulated after activation by serpins. SmSrpQ, one of two S. mansoni serpins found in larval secretions, is only expressed during larval development and in the early stages of mammalian infection. In vitro, 35S-SmSrpQ was able to form an SDS-stable complex with a component of the larval lysate, but no complex was detected when 35S-SmSrpQ was incubated with several mammalian host proteases. Formation of a complex was sensitive to the protease active site inhibitors PMSF, Z-AAPF-CMK, and Z-AAPL-CMK. Western blot analysis of parasite lysates from different life stages detected a complex of comparable size to SmCE bound to SmSrpQ using anti-SmSrpQ or anti-SmCE antibodies. SmSrpQ and SmCE are located in adjacent but discrete compartments in the secretion glands of the parasite. Fluorescence immunohistochemical analysis of simulated infection showed co-localization of SmCE and SmSrpQ in host tissue suggesting a post release regulation of parasite protease activity during skin transversal. The results of this study suggest that cercarial elastase degradation of skin tissue is carefully regulated by SmSrpQ.

• Publication year

  2011

• Venue

  Journal of Biological Chemistry

• Publication date

  2011-12-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M111.313304PMID 22174417PMCID PMC3293575
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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