Gingipains from Porphyromonas gingivalis increase the chemotactic and respiratory burst-priming properties of the 77-amino-acid interleukin-8 variant
Gingipains from Porphyromonas gingivalis increase the chemotactic and respiratory burst-priming properties of the 77-amino-acid interleukin-8 variant
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DOI：
10.1128/iai.00618-07
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Griffiths, Helen R.
中科院分区：
文献类型：
--
作者：
Dias, Irundika H. K.;Marshall, Lindsay;Griffiths, Helen R.
牙龈卟啉单胞菌是一种与活动性牙周炎病因相关的革兰氏阴性厌氧菌，它分泌降解酶（牙龈蛋白酶）并释放促炎介质（例如脂多糖[LPS]）。LPS触发免疫细胞（72个氨基酸[aa]变体[IL - 8(72aa)]）和非免疫细胞（IL - 8(77aa)）分泌白细胞介素 - 8（IL - 8）。IL - 8(77aa)具有较低的趋化性和呼吸爆发诱导活性，但易被牙龈蛋白酶切割。本研究表明，用R - 牙龈蛋白酶和K - 牙龈蛋白酶处理IL - 8(77aa)，可显著增强甲酰甲硫氨酰 - 亮氨酰 - 苯丙氨酸（fMLP）诱导的呼吸爆发激活和趋化活性（P < 0.05），但会降低IL - 8(72aa)对类中性粒细胞HL60细胞和原代中性粒细胞的呼吸爆发激活和趋化活性（P < 0.05）。通过串联质谱法，我们已经证明R - 牙龈蛋白酶从IL - 8(77aa)的N端部分切割下5个和11个氨基酸的肽段，所得肽段具有生物活性，而K - 牙龈蛋白酶去除一个8个氨基酸的N端肽段，产生一个69个氨基酸的IL - 8异构体，其生物活性增强。在牙周炎期间，根据趋化因子的细胞来源，分泌的牙龈蛋白酶可能对中性粒细胞针对IL - 8的趋化和激活产生不同的影响。
Porphyromonas gingivalis, a gram-negative anaerobe which is implicated in the etiology of active periodontitis, secretes degradative enzymes (gingipains) and sheds proinflammatory mediators (e.g., lipopolysaccharides [LPS]). LPS triggers the secretion of interleukin-8 (IL-8) from immune (72-amino-acid [aa] variant [IL-8(72aa)]) and nonimmune (IL-8(77aa)) cells. IL-8(77aa) has low chemotactic and respiratory burst-inducing activity but is susceptible to cleavage by gingipains. This study shows that both R- and K-gingipain treatments of IL-8(77aa) significantly enhance burst activation by fMLP and chemotactic activity (P < 0.05) but decrease burst activation and chemotactic activity of IL-8(72aa) toward neutrophil-like HL60 cells and primary neutrophils (P < 0.05). Using tandem mass spectrometry, we have demonstrated that R-gingipain cleaves 5- and 11-aa peptides from the N-terminal portion of IL-8(77aa) and the resultant peptides are biologically active, while K-gingipain removes an 8-aa N-terminal peptide yielding a 69-aa isoform of IL-8 that shows enhanced biological activity. During periodontitis, secreted gingipains may differentially affect neutrophil chemotaxis and activation in response to IL-8 according to the cellular source of the chemokine.