PMID- 32024243
OWN - NLM
STAT- MEDLINE
DCOM- 20210226
LR  - 20210226
IS  - 2072-6651 (Electronic)
IS  - 2072-6651 (Linking)
VI  - 12
IP  - 2
DP  - 2020 Feb 2
TI  - Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops 
      atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane 
      Components.
LID - 10.3390/toxins12020096 [doi]
LID - 96
AB  - 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 mug), for assessment 
      of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, 
      representing an increase of ~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.
FAU - Almeida, Michelle Teixeira de
AU  - Almeida MT
AD  - Programa de Pos-Graduacao em Ciencias-Toxinologia, Instituto Butantan, Sao Paulo 
      05503-900, Brazil.
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
FAU - Freitas-de-Sousa, Luciana Aparecida
AU  - Freitas-de-Sousa LA
AUID- ORCID: 0000-0002-4426-0731
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
FAU - Colombini, Monica
AU  - Colombini M
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
FAU - Gimenes, Sarah N C
AU  - Gimenes SNC
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
FAU - Kitano, Eduardo S
AU  - Kitano ES
AD  - Laboratorio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell 
      Signalig, CeTICS, Instituto Butantan, Sao Paulo 05503-900, Brazil.
FAU - Faquim-Mauro, Eliana L
AU  - Faquim-Mauro EL
AUID- ORCID: 0000-0001-8083-4272
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
FAU - Serrano, Solange M T
AU  - Serrano SMT
AD  - Laboratorio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell 
      Signalig, CeTICS, Instituto Butantan, Sao Paulo 05503-900, Brazil.
FAU - Moura-da-Silva, Ana Maria
AU  - Moura-da-Silva AM
AUID- ORCID: 0000-0003-1787-6634
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
LA  - eng
GR  - 2016/50127-5; 2014/26058-8; 2013/07467-1/Fundacao de Amparo a Pesquisa do Estado 
      de Sao Paulo/International
GR  - 303958/2018-9; 308133/2015-3/Conselho Nacional de Desenvolvimento Cientifico e 
      Tecnologico/International
GR  - 063/2010 Toxinology, AUXPE 1209/2011/Coordenacao de Aperfeicoamento de Pessoal de 
      Nivel Superior/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200202
PL  - Switzerland
TA  - Toxins (Basel)
JT  - Toxins
JID - 101530765
RN  - 0 (Crotalid Venoms)
RN  - 0 (Cytokines)
RN  - EC 3.4.- (Metalloproteases)
SB  - IM
MH  - Animals
MH  - Basement Membrane
MH  - *Bothrops
MH  - Crotalid Venoms/*enzymology
MH  - Cytokines/immunology
MH  - Edema/immunology
MH  - Hydrolysis
MH  - Leukocyte Count
MH  - Male
MH  - Metalloproteases/*toxicity
MH  - Mice, Inbred BALB C
MH  - Peritoneal Cavity
PMC - PMC7076977
OTO - NOTNLM
OT  - Bothrops atrox
OT  - SVMPs
OT  - basal membrane
OT  - hydrolysis
OT  - inflammation
OT  - metalloproteinases
OT  - peptides
COIS- The authors declare no conflicts of interest.
EDAT- 2020/02/07 06:00
MHDA- 2021/02/27 06:00
PMCR- 2020/02/01
CRDT- 2020/02/07 06:00
PHST- 2019/12/11 00:00 [received]
PHST- 2020/01/21 00:00 [revised]
PHST- 2020/01/30 00:00 [accepted]
PHST- 2020/02/07 06:00 [entrez]
PHST- 2020/02/07 06:00 [pubmed]
PHST- 2021/02/27 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - toxins12020096 [pii]
AID - toxins-12-00096 [pii]
AID - 10.3390/toxins12020096 [doi]
PST - epublish
SO  - Toxins (Basel). 2020 Feb 2;12(2):96. doi: 10.3390/toxins12020096.