Role of the major toxic components from Vipera ammodytes venom in its immunogenicity with special emphasis on hemorrhagic metalloproteinases

Kurtović, Tihana (2013) Role of the major toxic components from Vipera ammodytes venom in its immunogenicity with special emphasis on hemorrhagic metalloproteinases. Doctoral thesis, Faculty of Science > Department of Biology.

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Abstract

The venom of horn-nosed viper (Vipera a. ammodytes) has been used as an antigen for the production of antivenom against European vipers. In contrast to the detailed knowledge on structural and functional properties of ammodytoxins and hemorrhagins as its main toxic components, almost nothing has been known about their immunogenicity. Our research goal was to prepare the rabbit antisera containing antibodies specific for both classes of the pathology-inducing venom constituents and to evaluate the involvement of the obtained antibodies in neutralisation of the whole venom toxicity in mice. According to ED50 test, the only regulatory approved assay for the estimation of antivenom potency, fully functional antibodies specific for ammodytoxins participate in neutralisation of the whole venom's lethal toxicity only partially. Antibodies specific for hemorrhagins are not protective at all, despite their sufficiency in neutralisation of the local hemorrhagic effect in vivo. Furthermore, since hemorrhage as the prevalent clinical manifestation of envenoming in human is due to action of Zn2+-dependent metalloproteinases, structural and functional characterisation of the group representative, named ammodytagin, was of special research interest. Also, role of antibodies specific for individual protein exhibiting hemorrhagic phenotype in neutralisation of the whole venom hemorrhagicity was defined. Ammodytagin is a glycosylated, slightly acidic heterodimer of 108 kDa with multidomain organisation unique for members of P-IIIc subgroup which is characterised as enzyme of broad proteolytic specificity. The novel protein also acts as a strong hemorrhagin. Investigation of a substrate specificity revealed that hemorrhagic activity of ammodytagin might be the result of its involvement in cleavage of basal membrane components and depletion of coagulation factors in blood circulation. Finally, antiserum raised against ammodytagin was able to completely neutralise the hemorrhagic activity of the whole venom, suggesting it might be one of the key molecules towards which effective antivenom should be directed.

Item Type: Thesis (Doctoral thesis)
Keywords: horn-nosed viper venom, toxic components, ammodytoxins, hemorrhagins, protective efficacy, Zn2+-dependent metalloproteinase
Supervisor: Halassy, Beata
Date: 2013
Number of Pages: 150
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 29 Sep 2014 10:11
Last Modified: 29 Sep 2014 10:11
URI: http://digre.pmf.unizg.hr/id/eprint/2854

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