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Thromb Haemost 2005; 93(02): 359-367
DOI: 10.1160/TH04-05-0319
Cellular Proteolysis and Oncology
Schattauer GmbH

Identification and characterization of the plasma kallikrein-kinin system inhibitor, haemaphysalin, from hard tick, Haemaphysalis longicornis

Noriko Kato
1   Laboratory of Chemistry and Utilization of Animal Resources, Faculty of Agriculture, Kobe University, Kobe, Japan,
,
Shiroh Iwanaga
1   Laboratory of Chemistry and Utilization of Animal Resources, Faculty of Agriculture, Kobe University, Kobe, Japan,
,
Takahide Okayama
1   Laboratory of Chemistry and Utilization of Animal Resources, Faculty of Agriculture, Kobe University, Kobe, Japan,
,
Haruhiko Isawa
2   Laboratory of Physiology and Biochemistry, Department of Medical Entomology, National Institute of Infectious Diseases, Tokyo, Japan,
,
Masao Yuda
3   Department of Medical Zoology, School of Medicine, Mie University, Tsu, Japan
,
Yasuo Chinzei
3   Department of Medical Zoology, School of Medicine, Mie University, Tsu, Japan
› Author AffiliationsFinancial support: This study was supported from the Japan Society for Promoting Science (JSPS): Future Developmental Research (to Y. C.) and Young Scientists Fellowship B (to S. I.).
Further Information

Publication History

Received 21 May 2004

Accepted after revision 29 January 2004

Publication Date:
11 December 2017 (online)

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Summary

The plasma kallikrein-kinin system inhibitor, haemaphysalin, from the hard tick, Haemaphysalis longicornis, was identified. It was found that haemaphysalin inhibited activation of the plasma kallikrein-kinin system by interfering with reciprocal activation between factor XII and prekallikrein. It did not, however, inhibit amidolytic activities of factor XIIa and kallikrein. Direct binding assay indicated that factor XII/XIIa and high molecular weight kininogen (HK) are the target molecules of haemaphysalin, and that Zn2+ ions are involved in the interactions of haemaphysalin with these target molecules. This suggests that haemaphysalin interacts with target molecules by recognizing their conformational changes induced by Zn2+ ions. Furthermore, haemaphysalin interacted with the fibronectin type II domain and domain D5, the cell binding domains of factor XII and HK, respectively. This finding suggests that haemaphysalin interferes with the association of factor XII and the prekallikrein-HK complex with a biologic activating surface by binding to these cell-binding domains, leading to inhibition of the reciprocal activation between factor XII and prekallikrein.

Keywords

Kunitz-type protease inhibitor - plasma kallikrein-kinin system - tick - salivary gland
 

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