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Abstract

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.

Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components

“…Studies using MMP inhibitors have already confirmed the importance of the catalytic activity for the proinflammatory activity of SVMPs in experimental mice models. Leukocyte infiltrates induced by Jararhagin or BaP1 were reduced by treatments with chelating agents, such as o-phenanthroline or EDTA, respectively [8,35]. Escalante et al [5] tested the action of Batimastat, a broad-spectrum synthetic inhibitor of MMPs, in local damage induced by BaP1 and observed a reduction in bleeding, dermonecrosis and edema in mouse models.…”

“…SVMPs are zinc-dependent enzymes, classified in three classes, based on their precursors: the PI-class is composed of the pre-, pro-and metalloproteinase domains; PII-class of pre-, pro-, metalloproteinase and disintegrin domains; and PIII-class composed of pre-, pro-, metalloproteinase, disintegrin-like and cysteine-rich domains [4]. The PI-and PIII-classes are widely expressed in viper venoms and well characterized for their proinflammatory action, which is frequently associated with their catalytic activity [5][6][7] or with the activation of inflammatory cells as macrophages that release proinflammatory mediators [8,9]. Due to their catalytic activity, SVMPs may also have action on endogenous pro-metalloproteinases and pro-cytokines, such as pro-MMPs [10] and pro-TNF-α [11], which, upon cleavage by SVMPs, are released in their active form.…”

Pulmonary Inflammation and Edema Induced by Phospholipase A2

“…This observation led us to investigate the proinflammatory and edema-inducing properties of nsPLA 2 . Whereas these effects are known (14,37,38), little had been done to decipher the molecular determinants involved in venom PLA 2 -induced inflammation and edema, especially in the lungs.…”

Pro and Antiinflammatory Properties of Toxins from Animal Venoms

“…The toxin evoked local migration of leukocytes dependent on macrophages, since injection of the toxin in 1 hr pouches, absent of resident cells, did not induce cellular influx. This pattern of response is reversed by co-injection of peritoneal macrophages with the toxin into the cavity [146]. Jarastatin, a disintegrin RGD containing peptide rich in cystein domains isolated from Bj snakes, is chemotactic to neutrophil in vitro by interfering with intracellular locomotion machinery.…”