Examination of the Efficacy and Cross-Reactivity of a Novel Polyclonal Antibody Targeting the Disintegrin Domain in SVMPs to Neutralize Snake Venom.
Examination of the Efficacy and Cross-Reactivity of a Novel Polyclonal Antibody Targeting the Disintegrin Domain in SVMPs to Neutralize Snake Venom.
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DOI：
10.3390/toxins13040254
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发表时间：
2021-03-31
期刊：
影响因子：
4.2
通讯作者：
Galan JA
中科院分区：
文献类型：
--
作者：
Szteiter SS;Diego IN;Ortegon J;Salinas EM;Cirilo A;Reyes A;Sanchez O;Suntravat M;Salazar E;Sánchez EE;Galan JA
蛇毒可导致出血、局部坏死、肿胀，如果治疗不当，可导致不良全身效应，如凝血病、肾毒性、神经毒性和心脏毒性，可导致死亡。因此，蛇毒金属蛋白酶（SVMP）和去整合素是两种有毒成分，有助于出血和干扰止血系统。商业抗蛇毒血清的管理是常见的解毒剂来治疗蛇毒，但高成本，缺乏疗效，副作用，和有限的可用性，有必要开发新的策略和治疗方法。在此，我们描述了抗去整合素多克隆抗体对分离的去整合素、P-II/P-III SVMP和粗毒液的活性的中和能力。我们的研究结果表明去整合素对全血中血小板聚集和SK-Mel-28细胞的迁移的活性，其可以被抗去整合素多克隆抗体中和。我们表征了SVMP，并发现抗去整合素也能够在体外蛋白水解测定中抑制其活性。此外，我们发现抗去整合素可以中和粗响尾蛇毒的蛋白水解和出血活性。我们的研究结果表明，抗去整合素多克隆抗体有可能成为一种有针对性的方法，以中和SVMP在蛇咬伤envenomations的治疗。
Snake envenomation can result in hemorrhage, local necrosis, swelling, and if not treated properly can lead to adverse systemic effects such as coagulopathy, nephrotoxicity, neurotoxicity, and cardiotoxicity, which can result in death. As such, snake venom metalloproteinases (SVMPs) and disintegrins are two toxic components that contribute to hemorrhage and interfere with the hemostatic system. Administration of a commercial antivenom is the common antidote to treat snake envenomation, but the high-cost, lack of efficacy, side effects, and limited availability, necessitates the development of new strategies and approaches for therapeutic treatments. Herein, we describe the neutralization ability of anti-disintegrin polyclonal antibody on the activities of isolated disintegrins, P-II/P-III SVMPs, and crude venoms. Our results show disintegrin activity on platelet aggregation in whole blood and the migration of the SK-Mel-28 cells that can be neutralized with anti-disintegrin polyclonal antibody. We characterized a SVMP and found that anti-disintegrin was also able to inhibit its activity in an in vitro proteolytic assay. Moreover, we found that anti-disintegrin could neutralize the proteolytic and hemorrhagic activities from crude Crotalus atrox venom. Our results suggest that anti-disintegrin polyclonal antibodies have the potential for a targeted approach to neutralize SVMPs in the treatment of snakebite envenomations.
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影响因子：
3.3
作者：
Lauridsen, Line P.;Laustsen, Andreas H.;Maria Gutierrez, Jose
通讯作者：
Maria Gutierrez, Jose
影响因子：
2.8
作者：
HUANG, SY;PEREZ, JC
通讯作者：
PEREZ, JC
影响因子：
2.8
作者：
Calvete, JJ;Marcinkiewicz, C;Sanz, L
通讯作者：
Sanz, L
影响因子：
3.4
作者：
Bazaa, A;Marrakchi, N;Calvete, JJ
通讯作者：
Calvete, JJ
DOI：
10.1081/txr-120019018
发表时间：
2003-01-01
期刊：
JOURNAL OF TOXICOLOGY-TOXIN REVIEWS
影响因子：
--
作者：
Fry, BG;Winkel, KD;Wüster, W
通讯作者：
Wüster, W