A Blood Fluke Serine Protease Inhibitor Regulates an Endogenous Larval Elastase

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. manson...

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Bibliographic Details
Published in:The Journal of biological chemistry 2012-03, Vol.287 (10), p.7074-7083
Main Authors: Quezada, Landys A. Lopez, Sajid, Mohammed, Lim, Kee C., McKerrow, James H.
Format: Article
Language:English
Subjects:
Animals
Cysteine Proteinase Inhibitors - chemistry
Cysteine Proteinase Inhibitors - metabolism
Enzyme inhibitors
Helminth Proteins - chemistry
Helminth Proteins - metabolism
Host-Parasite Interactions - physiology
Larva - metabolism
Mammals - parasitology
Microbiology
Parasite
Parasitology
Schistosoma mansoni - physiology
Schistosomes
Schistosomiasis mansoni - metabolism
Schistosomiasis mansoni - pathology
Serine protease
Serpin
Serpins - chemistry
Serpins - metabolism
Snails - parasitology
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Summary: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. Schistosoma mansoni skin degradation is mediated by a serine protease, cercarial elastase (SmCE). A parasitic serpin, SmSrpQ, covalently binds to SmCE and is released into the host as the parasite penetrates the skin. SmSrpQ regulates the tissue-degrading activity of SmCE inside the host. SmSrpQ regulation of SmCE represents an important mechanism by which the parasite balances tissue penetration and host tissue damage.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.313304