Jararhagin disruption of endothelial cell anchorage is enhanced in collagen enriched matrices

Autor(es)

Baldo, C. ^[1] ; Lopes, D. S. ^[2] ; Faquim-Mauro, E. L. ^[1] ; Jacysyn, J. F. ^[3] ; Niland, S. ^[4] ; Eble, J. A. ^[4] ; Clissa, P. B. ^[1] ; Moura-da-Silva, A. M. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, Lab Imunopatol, BR-05503900 Sao Paulo, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Genet & Bioquim, BR-38400 Uberlandia, MG - Brazil

^[3] Univ Sao Paulo, Fac Med, LIM62, Sao Paulo, SP - Brazil

^[4] Univ Munster, Inst Physiol Chem & Pathobiochem, D-48149 Munster - Germany

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 108, p. 240-248, DEC 15 2015.
• Citações Web of Science: 9

Resumo

Hemorrhage is one of the most striking effects of bites by viper snakes resulting in fast bleeding and ischemia in affected tissues. Snake venom metalloproteinases (SVMPs) are responsible for hemorrhagic activity, but the mechanisms involved in SVMP-induced hemorrhage are not entirely understood and the study of such mechanisms greatly depends on in vivo experiments. In vivo, hemorrhagic SVMPs accumulate on basement membrane (BM) of venules and capillary vessels allowing the hydrolysis of collagen IV with consequent weakness and rupture of capillary walls. These effects are not reproducible in vitro with conventional endothelial cell cultures. In this study we used two-dimension (2D) or threedimension (3D) cultures of HUVECs on matrigel and observed the same characteristics as in ex vivo experiments: only the hemorrhagic toxin was able to localize on surfaces or internalize endothelial cells in 2D cultures or in the surface of tubules formed on 3D cultures. The contribution of matrigel, fibronectin and collagen matrices in jararhagin-induced endothelial cell damage was then analyzed. Collagen and matrigel substrates enhanced the endothelial cell damage induced by jararhagin allowing toxin binding to focal adhesions, disruption of stress fibers, detachment and apoptosis. The higher affinity of jararhagin to collagen than to fibronectin explains the localization of the toxin within BM. Moreover, once located in BM, interactions of jararhagin with alpha(2)beta(1) integrin would favor its localization on focal adhesions, as observed in our study. The accumulation of toxin in focal adhesions, observed only in cells grown in collagen matrices, would explain the enhancement of cell damage in these matrices and reflects the actual interaction among toxin, endothelial cells and BM components that occurs in vivo and results in the hemorrhagic lesions induced by viper venoms. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 09/09834-6 - Efeitos da interação entre células endoteliais e jararagina em culturas tridimensionais ricas em colágeno.
• Beneficiário: Cristiani Baldo da Rocha
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/16277-9 - Variabilidade na composição dos venenos botrópicos e implicações funcionais da presença de diferentes metaloproteinases na composição dos mesmos
• Beneficiário: Ana Maria Moura da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular