Imamura Takahisa
Division of Molecular Pathology, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
J Periodontol. 2003 Jan;74(1):111-8. doi: 10.1902/jop.2003.74.1.111.
Gingipains are trypsin-like cysteine proteinases produced by Porphyromonas gingivalis, a major causative bacterium of adult periodontitis. HRgpA (95 kDa) and RgpB (50 kDa), products of 2 distinct but related genes, rgpA and rgpB, respectively, are specific for Arg-Xaa peptide bonds. Kgp, a product of the kgp gene, is specific for Lys-Xaa bonds. HRgpA and Kgp are non-covalent complexes containing separate catalytic and adhesion/ hemagglutinin domains, while RgpB has only a catalytic domain with a primary structure essentially identical to that of the catalytic subunit of HRgp. HRgpA and RgpB induce vascular permeability enhancement through activation of the kallikrein/kinin pathway and activate the blood coagulation system, which, respectively, are potentially associated with gingival crevicular fluid production and progression of inflammation leading to alveolar bone loss in the periodontitis site. Kgp is the most potent fibrinogen/fibrin degrading enzyme of the 3 gingipains in human plasma and is involved in the bleeding tendency at the diseased gingiva. HRgpA activates coagulation factors and degrades fibrinogen/fibrin more efficiently than RgpB due to the adhesion/hemagglutinin domains, which have affinity for phospholipids and fibrinogen. Gingipains degrade macrophage CD14, thus inhibiting activation of the leukocytes through the lipopolysaccharide (LPS) receptor, and thereby facilitating sustained colonization of P. gingivalis. Gingipains play a role in bacterial housekeeping and infection, including amino acid uptake from host proteins and fimbriae maturation. Based on the important activities of gingipains in the bacterial infection and the pathogenesis of periodontitis, the bacterial proteinases can be targets for periodontal disease therapy. Immunization with RgpB, HRgpA, or a portion of HRgpA catalytic domain attenuated P. gingivalis induced disorders in mice. In addition, a trypsin-like proteinase inhibitor retarded P. gingivalis growth specifically. Gingipains are potent virulence factors of P. gingivalis, and are likely to be associated with the development of periodontitis. It is, therefore, suggested that gingipain inhibition by vaccination and gingipain-specific inhibitors is a useful therapy for adult periodontitis caused by P. gingivalis infection.
牙龈蛋白酶是由牙龈卟啉单胞菌产生的类胰蛋白酶半胱氨酸蛋白酶，牙龈卟啉单胞菌是成人牙周炎的主要致病菌。HRgpA（95 kDa）和RgpB（50 kDa）分别是两个不同但相关基因rgpA和rgpB的产物，它们对精氨酸-Xaa肽键具有特异性。Kgp是kgp基因的产物，对赖氨酸-Xaa键具有特异性。HRgpA和Kgp是非共价复合物，包含独立的催化结构域和粘附/血凝素结构域，而RgpB只有一个催化结构域，其一级结构与HRgp催化亚基的一级结构基本相同。HRgpA和RgpB通过激活激肽释放酶/激肽途径诱导血管通透性增强，并激活凝血系统，这分别可能与龈沟液产生以及导致牙周炎部位牙槽骨丧失的炎症进展有关。Kgp是人类血浆中三种牙龈蛋白酶中最有效的纤维蛋白原/纤维蛋白降解酶，与患病牙龈的出血倾向有关。由于具有对磷脂和纤维蛋白原的亲和力的粘附/血凝素结构域，HRgpA比RgpB更有效地激活凝血因子并降解纤维蛋白原/纤维蛋白。牙龈蛋白酶降解巨噬细胞CD-14，从而通过脂多糖（LPS）受体抑制白细胞的激活，进而促进牙龈卟啉单胞菌的持续定植。牙龈蛋白酶在细菌的正常代谢和感染中发挥作用，包括从宿主蛋白摄取氨基酸和菌毛成熟。基于牙龈蛋白酶在细菌感染和牙周炎发病机制中的重要作用，这些细菌蛋白酶可成为牙周疾病治疗的靶点。用RgpB、HRgpA或HRgpA催化结构域的一部分进行免疫可减轻牙龈卟啉单胞菌在小鼠中诱导的病症。此外，一种类胰蛋白酶抑制剂可特异性地抑制牙龈卟啉单胞菌的生长。牙龈蛋白酶是牙龈卟啉单胞菌的强效毒力因子，可能与牙周炎的发展有关。因此，建议通过疫苗接种抑制牙龈蛋白酶以及使用牙龈蛋白酶特异性抑制剂是治疗由牙龈卟啉单胞菌感染引起的成人牙周炎的有效方法。
