Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway

Rucavado, Alexandra; Nicolau, Carolina A.; Escalante, Teresa; Kim, Junho; Herrera, Cristina; Gutiérrez, José María; Fox, Jay W.

doi:10.3390/toxins8120349

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Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway

^1,†,

^2,†,

¹,

³,

^1,4,

^1,*

and

Jay W. Fox

^5,*

Instituto Clodomiro Picado, Facultad de Microbiología Universidad de Costa Rica, San José 11501-2060, Costa Rica

Laboratório de Toxinologia, Instituto Oswaldo Cruz, Rio de Janeiro CEP 21040-360, Brazil

Department of Fine Chemistry & New Materials, Sangji University, Wonju-si, Kangwon-do 220-702, Korea

⁴

Facultad de Farmacia, Universidad de Costa Rica, San José 11501-2060, Costa Rica

⁵

Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, P.O. Box 800734, Charlottesville, VA 22908, USA

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editor: R. Manjunatha Kini

Toxins 2016, 8(12), 349; https://doi.org/10.3390/toxins8120349

Received: 4 October 2016 / Revised: 15 November 2016 / Accepted: 17 November 2016 / Published: 24 November 2016

(This article belongs to the Special Issue Snake Venom Metalloproteinases)

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Abstract

Viperid snakebite envenomation is characterized by inflammatory events including increase in vascular permeability. A copious exudate is generated in tissue injected with venom, whose proteomics analysis has provided insights into the mechanisms of venom-induced tissue damage. Hereby it is reported that wound exudate itself has the ability to induce increase in vascular permeability in the skin of mice. Proteomics analysis of exudate revealed the presence of cytokines and chemokines, together with abundant damage associated molecular pattern molecules (DAMPs) resulting from both proteolysis of extracellular matrix and cellular lysis. Moreover, significant differences in the amounts of cytokines/chemokines and DAMPs were detected between exudates collected 1 h and 24 h after envenomation, thus highlighting a complex temporal dynamic in the composition of exudate. Pretreatment of mice with Eritoran, an antagonist of Toll-like receptor 4 (TLR4), significantly reduced the exudate-induced increase in vascular permeability, thus suggesting that DAMPs might be acting through this receptor. It is hypothesized that an “Envenomation-induced DAMPs cycle of tissue damage” may be operating in viperid snakebite envenomation through which venom-induced tissue damage generates a variety of DAMPs which may further expand tissue alterations. View Full-Text

Keywords: snake venom metalloproteinases (SVMPs); TLR4; damage associated molecular pattern molecules (DAMPs); exudate; increased vascular permeability

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MDPI and ACS Style

Rucavado, A.; Nicolau, C.A.; Escalante, T.; Kim, J.; Herrera, C.; Gutiérrez, J.M.; Fox, J.W. Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway. Toxins 2016, 8, 349. https://doi.org/10.3390/toxins8120349

AMA Style

Rucavado A, Nicolau CA, Escalante T, Kim J, Herrera C, Gutiérrez JM, Fox JW. Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway. Toxins. 2016; 8(12):349. https://doi.org/10.3390/toxins8120349

Chicago/Turabian Style

Rucavado, Alexandra, Carolina A. Nicolau, Teresa Escalante, Junho Kim, Cristina Herrera, José M. Gutiérrez, and Jay W. Fox. 2016. "Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway" Toxins 8, no. 12: 349. https://doi.org/10.3390/toxins8120349

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Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway

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