Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components

Autor(es)

Almeida, Michelle Teixeira de ^{[1, 2]} ; Freitas-de-Sousa, Luciana Aparecida ^[1] ; Colombini, Monica ^[1] ; Gimenes, Sarah N. C. ^[1] ; Kitano, Eduardo S. ^[3] ; Faquim-Mauro, Eliana L. ^[1] ; Serrano, Solange M. T. ^[3] ; Moura-da-Silva, Ana Maria ^[1]

Afiliação do(s) autor(es)

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

^[2] Inst Butantan, Programa Posgrad Ciencias Toxinol, BR-05503900 Sao Paulo - Brazil

^[3] Inst Butantan, Lab Toxinol Aplicada, Ctr Toxins Immune Response & Cell Signalig, CeTICS, BR-05503900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 12, n. 2 FEB 2020.
• Citações Web of Science: 8

Resumo

Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 mu g), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of similar to 70% of the paw size. Leukocyte infiltrates reached levels of 6 x 10(6) with ATXL and 5 x 10(6) with BATXH. TNF-alpha was identified in the supernatant of BATXH-or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC-MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4-5 x 10(6)) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in B. atrox envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways. (AU)

• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/50127-5 - Dimensions US-BIOTA São Paulo: scales of biodiversity: integrated studies of snake venom evolution and function across multiple levels of diversity
• Beneficiário: Inácio de Loiola Meirelles Junqueira de Azevedo
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 14/26058-8 - Inibição de metaloproteinases de mamíferos e de venenos de serpentes pelo pró-domínio recombinante da jararagina e seus fragmentos peptídicos
• Beneficiário: Ana Maria Moura da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular