Granzyme B: A New Crossroad of Complement and Apoptosis
Granzyme B: A New Crossroad of Complement and Apoptosis
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DOI：
10.1007/978-1-4614-0106-3_8
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发表时间：
2012-01-01
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影响因子：
--
通讯作者：
Huber-Lang, Markus
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文献类型：
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作者：
Perl, Mario;Denk, Stephanie;Huber-Lang, Markus
在严重的组织创伤中，几种“分子危险”传感和信号传导途径被激活，特别是补体和凋亡级联。虽然已经提出了两个系统之间可能的交叉点，但对潜在的分子相互作用知之甚少。在这项研究中，提出了一个新的相互作用界面的C3 a和C5 a的生成由促凋亡因子颗粒酶B。在体外孵育的中心人类补体成分C3和C5与丝氨酸蛋白酶颗粒酶B导致过敏毒素C3 a和C5 a的浓度依赖性生产。如此产生的过敏毒素C5a对分离的人中性粒细胞具有趋化活性。在翻译的方法，细胞内颗粒酶B浓度在白细胞中测定严重组织创伤后早期。与健康志愿者相比，多发性损伤患者（创伤后不到1小时，损伤严重度评分> 18，n = 5）中性粒细胞和淋巴细胞中的颗粒B水平显著增加。因此，组织创伤与补体和凋亡系统两者的早期激活有关。目前的数据表明，补体和细胞凋亡系统之间在颗粒酶B水平上的一种新的相互作用形式，其能够独立于已建立的补体蛋白酶产生C3 a和C5 a。
In response to severe tissue trauma, several "molecular danger" sensing and signaling pathways are activated, especially the complement and the apoptosis cascade. Although possible crossroads between both systems have been proposed, little is known about the underlying molecular interactions. In this study a new interaction interface is presented for C3a and C5a generation by the pro-apoptotic factor granzyme B. In vitro incubation of the central human complement components C3 and C5 with the serine protease granzyme B resulted in a concentration-dependent production of the anaphylatoxins C3a and C5a. The so generated anaphylatoxin C5a was chemotactic active for isolated human neutrophils. In a translational approach, intracellular granzyme B concentration in leukocytes was determined early after severe tissue trauma. In comparison to healthy volunteers, multiple injured patients (less than one hour after trauma, Injury Severity Score > 18, n = 5) presented a significant increase in granzmye B levels in neutrophils and lymphocytes. Thus, tissue trauma is associated with early activation of both, the complement and apoptosis system. The present data suggest a new form of interaction between the complement and the apoptosis system on the level of granzyme B that is capable to generate C3a and C5a independently of the established complement proteases.