Effects of two serine proteases from Bothrops pirajai snake venom on the complement system and the inflammatory response

Abstract

The present study aimed to evaluate the effects of two serine proteases from Bothrops pirajai snake venom, named BpirSP27 and BpirSP41, on the complement system and the inflammatory response. The effects of these enzymes on the human complement system were assessed by kinetic hemolytic assays, evaluating the hemolysis promoted by the classical/lectin (CP/LP) and alternative (AP) pathways after incubation of normal human serum with the serine proteases. The results suggested that these enzymes were able to induce modulation of CP/LP and AP at different levels: BpirSP41 showed higher inhibitory effects on the hemolytic activity of CP/LP than BpirSP27, with inhibition values close to 40% and 20%, respectively, for the highest concentration assayed. Regarding AP, both enzymes showed percentages of inhibition of the hemolytic activity around 20% for the highest concentrations tested, indicating similar effects on this complement pathway. The proinflammatory effects of B. pirajai serine proteases were evaluated regarding their ability to induce paw edema, variations in the pain threshold and leukocyte recruitment at the site of injection. Both showed mild effects on these inflammatory processes, leading to low levels of increase of paw volumes and decrease in pain thresholds in rats up to 6 h after injection, and inducing neutrophil recruitment without significant increases in the total number of leukocytes in the inflammatory exudates after 6 and 24 h of administration into mice peritoneal cavity. These results suggest that serine proteases must present a minor role in the inflammation caused by B. pirajai snake venom.

P-I Snake Venom Metalloproteinase Is Able to Activate the Complement System by Direct Cleavage of Central Components of the Cascade

“…Complement activation by an animal's toxin and its role in the envenomation remains poorly studied, but has been described for some snake venoms belonging to the Elapidae and Viperidae families [27]–[33], [19].…”

Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom

“…injection and releasing important inflammatory mediators such as the eicosanoids PGD 2 , PGE 2 , TXA 2 , LTB 4 , the cytokines TNF-α, IL-6, IL-10, and the chemokine CCL-2 [52]. These inflammatory effects are most commonly related to phospholipases A 2 and metalloproteinases [72,73], although other classes of enzymes may also contribute to these responses [49].…”

Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2) Involves the PAR Pathway and PKC and PLC Activation

“…All SVSPs identified to date present a catalytic triad comprising histidine (His), aspartate (Asp), and serine (Ser), essential for their enzyme activity [2,5]. Recent studies strongly suggested that serine proteases BpirSP27 and BpirSP41, purified from Bothrops pirajai (Bpir), were able to activate the complement system, potentially inducing edema under experimental conditions, and may include proinflammatory features, as well as being significantly inhibited by nonsteroidal anti-inflammatory drugs [6,7,8]. Other SVSPs purified from Bothrops alternatus , Bothrops mooeni [9], Trimeresurus elegans , and Trimeresurus jerdonni venom revealed the ability to release kinin, as well as fibrinolytic and edematogenic activities [10].…”

“…The most stable product derived from the arachidonic pathway is prostaglandin E2 (PGE2). In addition, the presence of cell-surface receptors represents another essential feature of cPLA2,which stimulates the signaling pathways associated with the activation of protein kinases and the production of reactive oxygen species (ROS) [6,16,24]. …”