A novel coagulation inhibitor from Schistosoma japonicum

Ranasinghe, Shiwanthi L., Fischer, Katja, Gobert, Geoffrey N. and McManus, Donald P. (2015) A novel coagulation inhibitor from Schistosoma japonicum. Parasitology, 142 14: 1663-1672. doi:10.1017/S0031182015001328


Author Ranasinghe, Shiwanthi L.
Fischer, Katja
Gobert, Geoffrey N.
McManus, Donald P.
Title A novel coagulation inhibitor from Schistosoma japonicum
Journal name Parasitology   Check publisher's open access policy
ISSN 0031-1820
1469-8161
Publication date 2015-10-14
Year available 2015
Sub-type Article (original research)
DOI 10.1017/S0031182015001328
Open Access Status Not Open Access
Volume 142
Issue 14
Start page 1663
End page 1672
Total pages 10
Place of publication Cambridge, United Kingdom
Publisher Cambridge University Press
Collection year 2016
Language eng
Formatted abstract
Little is known about the molecular mechanisms whereby the human blood fluke Schistosoma japonicum is able to survive in the host venous blood system. Protease inhibitors are likely released by the parasite enabling it to avoid attack by host proteolytic enzymes and coagulation factors. Interrogation of the S. japonicum genomic sequence identified a gene, SjKI-1, homologous to that encoding a single domain Kunitz protein (Sjp_0020270) which we expressed in recombinant form in Escherichia coli and purified. SjKI-1 is highly transcribed in adult worms and eggs but its expression was very low in cercariae and schistosomula. In situ immunolocalization with anti-SjKI-1 rabbit antibodies showed the protein was present in eggs trapped in the infected mouse intestinal wall. In functional assays, SjKI-1 inhibited trypsin in the picomolar range and chymotrypsin, neutrophil elastase, FXa and plasma kallikrein in the nanomolar range. Furthermore, SjKI-1, at a concentration of 7·5 µm, prolonged 2-fold activated partial thromboplastin time of human blood coagulation. We also demonstrate that SjKI-1 has the ability to bind Ca++. We present, therefore, characterization of the first Kunitz protein from S. japonicum which we show has an anti-coagulant properties. In addition, its inhibition of neutrophil elastase indicates SjKI-1 have an anti-inflammatory role. Having anti-thrombotic properties, SjKI-1 may point the way towards novel treatment for hemostatic disorders.
Keyword Anticoagulant
Antiinflammatory agent
Kunitz protein
Trypsin Inhibitor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Public Health Publications
 
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