Neutrophils do not contribute to local tissue damage, but play a key role in skeletal muscle regeneration, in mice injected with Bothrops asper snake venom
Neutrophils do not contribute to local tissue damage, but play a key role in skeletal muscle regeneration, in mice injected with Bothrops asper snake venom
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DOI：
10.1002/mus.10453
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发表时间：
2003-10-01
期刊：
影响因子：
3.4
通讯作者：
Gutiérrez, JM
中科院分区：
文献类型：
--
作者：
Teixeira, CFP;Zamunér, SR;Gutiérrez, JM
响尾蛇蛇毒引起的局部组织损伤包括水肿、肌坏死、出血和与显著细胞浸润相关的炎症反应。本文研究了中性粒细胞在蝮蛇毒和从蝮蛇毒中分离的磷脂酶A（2）-肌毒素1（myotoxin 1）引起的局部组织损伤中的作用。用抗小鼠粒细胞大鼠单克隆免疫球蛋白G（IgG）抗体或同种型匹配的对照抗体对雄性瑞士小鼠进行预处理。在这些局部效应中，在用抗粒细胞抗体预处理的小鼠和接受对照IgG的小鼠之间没有观察到显著差异。此外，B. Asper肌毒素I在嗜中性粒细胞耗尽的小鼠和对照小鼠中相似。还评估了中性粒细胞在骨骼肌再生过程中的作用。通过定量肌酸激酶的肌肉水平和通过骨骼肌受损区域中再生细胞所包含的区域的形态学组织学分析来评估肌肉再生。小鼠耗尽中性粒细胞，然后注射B。与用对照IgG预处理的小鼠相比，蛇蛇毒显示出更缺乏的再生反应。此外，在注射肌毒素1的小鼠中观察到再生反应的显著差异，因为用对照IgG预处理的动物显示出成功的再生，而那些耗尽中性粒细胞的动物具有大量的坏死组织区域，这些坏死组织在注射后7天未被去除，这与肌酸激酶含量降低有关。结果表明：（1）中性粒细胞在B蛇毒引起的急性局部病理改变中不起重要作用。（2）中性粒细胞在B诱导的骨骼肌再生过程中起重要作用。曲霉毒素和肌毒素1，可能与坏死物质的吞噬作用和其他炎性细胞的募集有关，这两个事件与成功的肌肉再生反应直接相关。
Local tissue damage induced by crotaline snake venoms includes edema, myonecrosis, hemorrhage, and an inflammatory response associated with a prominent cellular infiltrate. The role of neutrophils in the local tissue damage induced by Bothrops asper snake venom and by myotoxin 1, a phospholipase A(2) isolated from this venom, was investigated. Male Swiss mice were pretreated with either an antimouse granulocyte rat monoclonal immunoglobulin G (IgG) antibody or with isotype-matched control antibody. No significant differences in these local effects were observed between mice pretreated with antigranulocyte antibodies and those receiving control IgG. Moreover, myotoxicity induced by B. asper myotoxin I was similar in neutrophil-depleted and control mice. The role of neutrophils in the process of skeletal muscle regeneration was also assessed. Muscle regeneration was assessed by quantifying the muscle levels of creatine kinase and by morphometric histological analysis of the area comprised by regenerating cells in damaged regions of skeletal muscle. Mice depleted of neutrophils and then injected with B. asper venom showed a more deficient regenerative response than mice pretreated with control IgG. Moreover, a drastic difference in the regenerative response was observed in mice injected with myotoxin 1, because animals pretreated with control IgG showed a successful regeneration, whereas those depleted of neutrophils had abundant areas of necrotic tissue that had not been removed 7 days after injection, associated with reduced contents of creatine kinase. It is concluded that (1) neutrophils do not play a significant role in the acute local pathological alterations induced by the venom of B. asper, and (2) neutrophils play a prominent role in the process of skeletal muscle regeneration after injection of B. aspervenom and myotoxin 1, probably related to the phagocytosis of necrotic material and the recruitment of other inflammatory cells, two events directly associated with a successful muscle regenerative response.