Importance of metalloproteinases and macrophages in viper snake envenomation-induced local inflammation.
The inflammatory action of jararhagin, a hemorrhagic metalloproteinase from Bothrops jararaca venom, was studied in mice using dorsal air pouches. The injection of the toxin in 6-day-old air pouches resulted in a leukocyte accumulation comparable to that induced by LPS and whole venom. Polymorphonuclear and mononuclear cells were present in this infiltrate, with a predominance of neutrophils. Treatment of jararhagin with 1,10-phenantroline abolished its proteolytic activity and reduced the pro-inflammatory effect in approximately 50%. Cell influx was not observed when jararhagin was injected into 1-hr air pouches devoid of macrophages, except when it was injected together with 10(6) syngeneic peritoneal macrophages. Supernatants of macrophages stimulated in vitro with jararhagin did not induce leukocyte influx in 1-hr air pouches; the influx occurred after injection of the pellets of stimulated cultures. In summary, jararhagin is an important pro-inflammatory component of B. jararaca venom, and its activity is dependent upon the proteolytic activity and the presence of macrophages.
Costa
E P
EP
Laboratório de Imunopatologia, Instituto Butantan, São Paulo, Brazil.
Clissa
P B
PB
Teixeira
C F P
CF
Moura-da-Silva
A M
AM
D000818:Animals; D017837:Bothrops; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014757:Viper Venoms / Q000008:administration & dosage / Q000201:enzymology / Q000494:pharmacology*
D014757:Viper Venoms; D008666:Metalloendopeptidases