Skin Pathology Induced by Snake Venom Metalloproteinase: Acute Damage, Revascularization, and Re-epithelization in a Mouse Ear Model

 

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Autores: Jiménez Álvarez, Natalia, Escalante Muñoz, Teresa, Gutiérrez, José María, Rucavado Romero, Alexandra
Formato: artículo original
Fecha de Publicación:2008
Descripción:Viperid snakebite envenomation induces blistering and dermonecrosis. The pathological alterations induced by a snake venom metalloproteinase in the skin were investigated in a mouse ear model. Metalloproteinase BaP1, from Bothrops asper, induced rapid edema, hemorrhage, and blistering; the latter two effects were abrogated by preincubation with the metalloproteinase inhibitor batimastat. Neutrophils did not play a role in the pathology, as depletion of these cells resulted in a similar histological picture. Blisters are likely to result from the direct proteolytic activity of BaP1 of proteins at the dermal-epidermal junction, probably at the lamina lucida, as revealed by immunostaining for type IV collagen and laminin. Widespread apoptosis of keratinocytes was detected by the TUNEL assay, whereas no apoptosis of capillary endothelial cells was observed. BaP1 induced a drastic reduction in the microvessel density, revealed by immunostaining for the endothelial marker vascular endothelial growth factor receptor-2. This was followed by a rapid angiogenic response, leading to a partial revascularization. Skin damage was followed by inflammation and granulation tissue formation. Then, a successful re-epithelization process occurred, and the skin of the ear regained its normal structure by 2 weeks. Venom metalloproteinase-induced skin damage reproduces the pathological changes described in snakebitten patients.
País:Kérwá
Institución:Universidad de Costa Rica
Repositorio:Kérwá
OAI Identifier:oai:https://www.kerwa.ucr.ac.cr:10669/29264
Acceso en línea:http://www.sciencedirect.com/science/article/pii/S0022202X15336356
https://hdl.handle.net/10669/29264
Access Level:acceso abierto
Palabra clave:Animals
Basement Membrane
Blister
Blood Vessels
Dermatitis, Contact
Disease Models, Animal
Ear
Epithelium
Granulation Tissue
Hemorrhage
Immunohistochemistry
In Situ Nick-End Labeling
Metalloendopeptidases
Mice
Inbred Strains
Microcirculation
Skin
Wound Healing