Expression of Human Recombinant Antibody Fragments Capable of Partially Inhibiting the Phospholypase Activity ofCrotalus durissus terrificusVenom
| Autor: | Juliana Graciela Giovannini Oliveira, José Elpídio Barbosa, Sandro Gomes Soares, José Roberto Giglio, Jose E. Teixeira, Andreimar M. Soares |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Phospholipase A2 Inhibitors Venom Phospholipase Biology Toxicology law.invention Mice Phospholipase A2 law In vivo Crotalid Venoms Animals Humans Envenomation Immunoglobulin Fragments Pharmacology Antibodies Monoclonal Biological activity General Medicine Crotoxin Recombinant Proteins In vitro Biochemistry Immunology Recombinant DNA biology.protein |
| Zdroj: | Basic & Clinical Pharmacology & Toxicology. 105:84-91 |
| ISSN: | 1742-7843 1742-7835 |
| DOI: | 10.1111/j.1742-7843.2008.00322.x |
| Popis: | Crotoxin is the main toxic component of the South American rattlesnake Crotalus durissus terrificus venom. It is composed of two different subunits: CA, crotapotin, and CB (basic subunit of cortoxin isolated from C. d. terrificus), a weakly toxic phospholipase A2 with high enzymatic activity. The phospholipases A2 are abundant in snake venoms and are responsible for disruption of cell membrane integrity via hydrolysis of its phospholipids. However, in addition to their normal digestive action, a wide range of pharmacological activities, such as neurotoxic, myotoxic, oedema-inducing, hypotensive, platelet-aggregating, cardiotoxic, and anticoagulant effects have been attributed to venom phospholipases A2. In this study, we used a non-immune human single-chain fragment variable library, Griffin.1 (Medical Research Council, Cambridge, UK) for selection of recombinant antibodies against antigens present in C. d. terrificus venom and identification of specific antibodies able to inhibit the phospholipase activity. Two clones were identified as capable of inhibiting partially this activity in vitro. These clones were able to reduce in vivo the myotoxic and oedema-inducing activity of CB and the lethality of C. d. terrificus venom and crotoxin, but had no effect on the in vitro anticoagulant activity of CB. These results demonstrate the potential of using recombinant single-chain fragment variable libraries in the production of antivenoms. |
| Databáze: | OpenAIRE |
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