Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis.
Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis.
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DOI：
10.1016/s0021-9258(19)37046-2
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发表时间：
1992-09
期刊：
影响因子：
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通讯作者：
J. Wingrove;R. Discipio;Z. Chen;J. Potempa;James Travis;T. E. Hugli
中科院分区：
文献类型：
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作者：
J. Wingrove;R. Discipio;Z. Chen;J. Potempa;James Travis;T. E. Hugli
补体成分C3和C5对从牙龈卟啉单胞菌分离的精氨酸特异性半胱氨酸蛋白酶进行有限的蛋白降解敏感。这种细菌是一种厌氧菌，通常与严重的牙周病有关。牙龈假单胞菌感染伴有急性炎症反应，并伴有广泛的中性粒细胞受累。这促使我们研究补体在牙周炎中可能的直接作用。当C3和C5与半胱氨酸蛋白酶的摩尔比为1：25和1：100(酶与底物的比例)时，C3和C5对每个组分的降解都是时间相关的，有限的。C3被逐步转化为类C3a和类C3b片段，并有证据表明分子中类C3a部分的广泛进一步降解。我们无法证明C3消化混合物中的C3a活性。C3的降解似乎主要涉及阿尔法链。C5的蛋白分解也以一种循序渐进的方式进行，产生阿尔法链的初始内部裂解，从而产生30和86 kDa的片段。α链86 kDa氨基末端片段的进一步消化导致C5a或对中性粒细胞激活具有生物活性的C5a类片段的释放。事实上，一种强有力的趋化因子，即C5a，可以由牙周病患者牙周疾病中的一种蛋白酶从C5产生，这表明了一种将中性粒细胞吸引到牙周病变部位的招募机制。
Complement components C3 and C5 are susceptible to limited proteolysis by an arginine-specific cysteine proteinase isolated from Porphyromonas gingivalis. This bacterium is an anaerobe commonly associated with severe periodontal disease. Infection by P. gingivalis is accompanied by an acute inflammatory response, complete with extensive neutrophil involvement. This prompted us to investigate a possible direct role for complement in periodontitis evoked by P. gingivalis. Exposure of C3 and C5 to the cysteine proteinase at molar ratios between 1:25 and 1:100 (enzyme to substrate ratios) resulted in a time-dependent, limited degradation of each component. C3 was converted in a stepwise manner to C3a-like and C3b-like fragments with evidence of extensive further degradation of the C3a-like portion of the molecule. We were unable to demonstrate C3a activity in the C3 digestion mixtures. C3 degradation appears to involve primarily the alpha-chain. Proteolysis of C5 also progresses in a stepwise manner producing an initial internal cleavage of the alpha-chain to generate 30- and 86-kDa fragments. Further digestion of the 86-kDa amino-terminal fragment of the alpha-chain leads to the release of C5a or a C5a-like fragment that is biologically active for neutrophil activation. The fact that a potent chemotactic factor, i.e. C5a, can be generated from C5 by a proteinase derived from P. gingivalis suggests a recruiting mechanism for attracting neutrophils to the gingival lesion site in periodontal disease.