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Inflammatory pathogenesis of snake venom metalloproteinase-induced skin necrosis

Laing, Gavin David, Clissa, Patricia Bianca, Theakston, R.David G., Moura-da-Silva, Ana Maria and Taylor, Mark John ORCID: https://orcid.org/0000-0003-3396-9275 (2003) 'Inflammatory pathogenesis of snake venom metalloproteinase-induced skin necrosis'. European Journal of Immunology, Vol 33, Issue 12, pp. 3458-3463.

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Abstract

Local tissue damage, characterized by edema, hemorrhage and necrosis, is a common consequence of envenoming by many vipers. We have investigated the contribution of inflammatory responses induced by the venom metalloproteinase jararhagin (isolated from Bothrops jararaca venom) in the development of these lesions. Local venom effects (edema, hemorrhage and necrosis) were induced experimentally in knockout mice deficient in the TNF receptors TNFR1 or TNFR2, IL-1betaR, IL-6 and NOS. Jararhagin-induced dermal necrosis was abolished in mice deficient in the TNF receptors TNFR1 and TNFR2, and the same activity was significantly reduced in IL-6(-/-) mice. There was no significant difference in edema and hemorrhage activities following jararhagin insult between knockout and WT strains, indicating that these local venom metalloproteinase-induced effects are independent of these pro-inflammatory mediators. The contribution of both TNF receptors and IL-6 in local tissue necrosis raises important therapeutic issues regarding the treatment of local envenoming.

Item Type: Article
Uncontrolled Keywords: Mouse;Cytokines;Inflammation;Knockout;Skin
Subjects: WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
WR Dermatology > WR 100 General works
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1002/eji.200324475
Depositing User: Ms Julia Martin
Date Deposited: 08 Jun 2012 08:22
Last Modified: 16 Sep 2019 09:01
URI: https://archive.lstmed.ac.uk/id/eprint/2583

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