Delayed local inflammatory response induced by Thalassophryne nattereri venom is related to extracellular matrix degradation.
Symptoms evoked by Thalassophryne nattereri fish envenomation include local oedema, severe pain and intense necrosis with strikingly inefficient healing, continuing for several weeks or months. Investigations carried out in our laboratory showed that, in the venom-induced acute inflammation, thrombosis in venules and constrictions in arterioles were highly visible, in contrast to a notable lack of inflammatory cell. Nevertheless, the reason that the venom toxins favour delayed local inflammatory response is poorly defined. In this study, we analysed the movement of leucocytes after T. nattereri venom injection in the intraplantar region of Swiss mice, the production of pro-inflammatory mediators and the venom potential to elicit matrix metalloproteinase production and extracellular matrix degradation. Total absence of mononuclear and neutrophil influx was observed until 14 days, but the venom stimulates pro-inflammatory mediator secretion. Matrix metalloproteinases (MMP)-2 and MMP-9 were detected in greater quantities, accompanied by tissue degradation of collagenous fibre. An influx of mononuclear cells was noted very late and at this time the levels of IL-6, IL-1beta and MMP-2 remained high. Additionally, the action of venom on the cytoskeletal organization was assessed in vitro. Swift F-actin disruption and subsequent loss of focal adhesion was noted. Collectively these findings show that the altered specific interaction cell-matrix during the inflammatory process creates an inadequate environment for infiltration of inflammatory cells.
Pareja-Santos
Alessandra
A
Special Laboratory of Applied Toxinology (CAT/CEPID), Butantan Institute, Butantan, Sao Paulo, Brazil.
Saraiva
Tania Cristina
TC
Costa
Erica Pereira
EP
Santos
Marinilce Fagundes
MF
Zorn
Telma Tenorio
TT
Souza
Valdenia Maria Oliveira
VM
Lopes-Ferreira
Monica
M
Lima
Carla
C
D000818:Animals; D024541:Batrachoidiformes / Q000378:metabolism*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005397:Fish Venoms / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice
D005397:Fish Venoms; D018836:Inflammation Mediators; D003094:Collagen; D020782:Matrix Metalloproteinases