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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: TOXINS; v. 12, n. 2 FEB 2020.
• Web of Science Citations: 8

Abstract

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)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/50127-5 - Dimensions US-BIOTA São Paulo: scales of biodiversity: integrated studies of snake venom evolution and function across multiple levels of diversity
• Grantee: Inácio de Loiola Meirelles Junqueira de Azevedo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 14/26058-8 - Inhibition of mammalian and snake venom metalloproteinases by the recombinant pro-domain of jararhagin and its relevant peptide fragments
• Grantee: Ana Maria Moura da Silva
• Support Opportunities: Regular Research Grants