Novel insights into capillary vessel basement membrane damage by snake venom hemorrhagic metalloproteinases: A biochemical and immunohistochemical study

 

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Autores: Escalante Muñoz, Teresa, Shannon, John D., Moura Da Silva, Ana M., Gutiérrez, José María, Fox, Jay W.
Formato: artículo original
Fecha de Publicación:2016
Descripción:The hemorrhagic activity characteristic of viperid snake envenomations is due to the action of venom metalloproteinases (SVMPs) on the capillary vessel basement membrane (BM). This study compared the action of two SVMPs on BM in vitro (degradation of Matrigel) and in vivo (immunohistochemical assessment of BM markers in mouse gastrocnemius muscle). SVMPs BaP1 (belonging to the P-I class) and jararhagin (of the P-III class) had a similar proteolytic activity on azocasein and degraded Matrigel with a slightly different cleavage pattern, since BaP1 exerted a limited proteolysis of both laminin and nidogen, whereas jararhagin predominantly degraded nidogen. In contrast with this pattern of limited proteolysis of BM proteins observed in vitro, immunohistochemical analysis of laminin, nidogen and type IV collagen, as well as of the endothelial cell marker VEGFR-2, in the hemorrhagic areas in the muscle, revealed a pronounced reduction in the immunostaining of these three BM components, associated with a loss of the endothelial cell marker. BM of muscle fibers was affected to a lesser extent. In conclusion, in vitro results demonstrated that SVMPs induce a pattern of limited proteolysis on BM components. The drastic loss of these antigens in affected capillaries in vivo is likely to depend on the combination of limited proteolysis of BM and the action of hemodynamic biophysical forces, previously shown to play a role in SVMP-induced capillary damage, which may cause a mechanical disruption of BM structure.
País:Kérwá
Institución:Universidad de Costa Rica
Repositorio:Kérwá
OAI Identifier:oai:https://www.kerwa.ucr.ac.cr:10669/29387
Acceso en línea:http://www.sciencedirect.com/science/article/pii/S0003986106003547
https://hdl.handle.net/10669/29387
Access Level:acceso abierto
Palabra clave:Metalloproteinase
Basement Membrane
Endothelial Cells
Hemorrhage
Extracellular Matrix
Snake venom