Contribution of metalloproteases, serine proteases and phospholipases A2 to the inflammatory reaction induced by Bothrops jararaca crude venom in mice
Contribution of metalloproteases, serine proteases and phospholipases A2 to the inflammatory reaction induced by Bothrops jararaca crude venom in mice
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DOI：
10.1016/j.toxicon.2009.07.025
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发表时间：
2010-02-01
期刊：
影响因子：
2.8
通讯作者：
Goncalves, Luis Roberto C.
中科院分区：
文献类型：
--
作者：
Zychar, Bianca Cestari;Dale, Camila Squazoni;Goncalves, Luis Roberto C.
从Bothrops蛇毒中分离出的各种毒素会引起炎症反应，并被认为会导致这种毒液中毒中局部症状的严重程度。尽管如此，丝氨酸蛋白酶、金属蛋白酶和磷脂酶A（2）在粗Bothrops毒液产生的炎症反应中的相对参与程度仍知之甚少。本文中，粗Bothrops jararaca毒液用苯甲磺酰氟（PMSF）、1，10-菲咯啉（oPhe）或对溴苯甲酰甲基溴（p-BPB）处理以分别抑制那些类别的酶，并且评估炎症参数并与由对照粗毒液诱导的那些进行比较。水肿和痛觉过敏/异常性疼痛的强度显着降低与oPhe处理的毒液管理的动物。白细胞-内皮细胞相互作用（LEI），如白细胞的粘附和迁移，也在2 h和24 h改变。p-BPB处理的毒液引起的水肿和LEI参数与对照毒液观察到的相似，但痛觉过敏异常性疼痛显着降低。由PMSF处理的毒液诱导的炎症参数与由粗毒液诱导的那些相似，除了水肿强度轻度降低。我们的研究结果表明，金属蛋白酶在B诱导的炎症反应中具有关键作用。jararaca毒液，磷脂酶A（2）和丝氨酸蛋白酶具有次要作用。(C)2009爱思唯尔有限公司保留所有权利。
Various toxins isolated from Bothrops snake venoms induce inflammatory reactions and have been claimed to contribute to the severity of local symptoms present in this envenomation. Notwithstanding, the relative participation of serine proteases, metal-loproteases and phospholipases A(2) in the inflammatory reaction produced by crude Bothrops venoms is poorly understood. Herein, crude Bothrops jararaca venom was treated with phenylmethanesulfonyl fluoride (PMSF), 1,10-phenanthroline (oPhe), or p-bromophenacyl-bromide (p-BPB) to inhibit those classes of enzymes, respectively, and inflammatory parameters were evaluated and compared to those induced by the control crude venom. The intensity of edema and hyperalgesia/allodynia was remarkably reduced in animals administered with oPhe-treated venom. Leukocyte-endothelium interactions (LEI), such as adhesion and migration of leukocytes, were also modified at 2 h and 24 h. Edema and LEI parameters induced by p-BPB-treated venom were similar to those observed with the control venom, but hyperalgesial-allodynia was significantly lower. Inflammatory parameters induced by PMSF-treated venom were similar to those induced by the crude venom, except for a mild reduction in edema intensity. Our results indicate that metal I oproteases have a pivotal role in the inflammatory reactions induced by B. jararaca venom, and phospholipases A(2) and serine proteases have a minor role. (C) 2009 Elsevier Ltd. All rights reserved.