title: Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway.
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.
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología Universidad de Costa Rica, San José 11501-2060, Costa Rica. alexandra.rucavado@ucr.ac.cr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rucavado
authors.affiliation: Laboratório de Toxinologia, Instituto Oswaldo Cruz, Rio de Janeiro CEP 21040-360, Brazil. carolnicolau.bio@gmail.com.
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Nicolau
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología Universidad de Costa Rica, San José 11501-2060, Costa Rica. teresa.escalante@ucr.ac.cr.
authors.forename: Teresa
authors.initials: T
authors.lastname: Escalante
authors.affiliation: Department of Fine Chemistry & New Materials, Sangji University, Wonju-si, Kangwon-do 220-702, Korea. jhokim@sangji.ac.kr.
authors.forename: Junho
authors.initials: J
authors.lastname: Kim
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología Universidad de Costa Rica, San José 11501-2060, Costa Rica. cristina.herreraarias@gmail.com.|Facultad de Farmacia, Universidad de Costa Rica, San José 11501-2060, Costa Rica. cristina.herreraarias@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Herrera
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología Universidad de Costa Rica, San José 11501-2060, Costa Rica. jose.gutierrez@ucr.ac.cr.
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, P.O. Box 800734, Charlottesville, VA 22908, USA. jwf8x@eservices.virginia.edu.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Fox
mesh_terms: D000067531:Alarmins / Q000378:metabolism; D000818:Animals; D017837:Bothrops; D002199:Capillary Permeability; D003435:Crotalid Venoms / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D005122:Exudates and Transudates / Q000378:metabolism*; D051379:Mice; D040901:Proteomics; D012909:Snake Bites / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000067531:Alarmins; D003435:Crotalid Venoms; D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: TLR4; damage associated molecular pattern molecules (DAMPs); exudate; increased vascular permeability; snake venom metalloproteinases (SVMPs)