THE ROLE OF NATTERINS, MAJORITARY TOXINS OF THE Thalassophryne nattereri  FISH VENOM IN LOCAL INFLAMMATORY RESPONSE IN MICE

PAREJA A., LOPES-FERREIRA M., LIMA C.(1)

(1)Laboratory Immunopatology, Institute Butantan

Natterins, isolated toxins from Thalassophryne nattereri (niquim) fish venom, is a family of 5 toxins which present homology amongst themselves and molecular mass around 30-45 kDa. The group of majority toxins Natterin 1, 2 and 3 was used for the evaluation of the inflammatory response in mice. The kinetic of the leukocyte recruitment, cytokine and chemokine levels and matrix metalloproteinases 2 and 9 activity after administration of Natterins in the footpad of Swiss mice was determined. After 6, 24 and 48 hours or 7, 14 and 21 days the animals injected with 10 microgram of Natterins were was sacrificed and the footpad was processed for cellular suspension collection and inflammatory mediators were determined in supernatant of footpad homogenates. The leukocyte cell counts were performed using a hemocytometer using Hema3-stained cytospin preparations. Natterins were not able to induce leukocyte influx into footpad of mice at 6 h after injection, that was characterized by a significant reduction of macrophages and lymphocytes compared with PBS-group, but after 7 days Natterins provoked an intense recruitment of neutrophils, macrophages, and lymphocytes. The footpad levels of PGD2, IL1-beta, IL-6, MCP-1 were augmented after 6 hours and IL1-beta and TNF-alpha after 7 days. High MMP-9 activity was detected in footpad supernatant at 6 h. We can suggest that the impared cellular influx provoked by Natterins was independently of cytokines or chemokines production, and it could be related with the high MMP-9 activity in the footpad.

KEY WORDS: Thalassophryne nattereri, venomous fishes, Natterins, inflammatory response.

FINANCIAL SUPPORT: FAPESP, FUNDAP.

CORRESPONDENCE TO: ALESSANDRA PAREJA, Laboratory Immunopatology, Institute Butantan, Av. Vital Brazil, 1500, Butantã, São Paulo, 05503-009, Brazil. Email: alepareja@butantan.gov.br; alessandra_pareja@yahoo.com.br.