Lah T T, Babnik J, Schiffmann E, Turk V, Skaleric U
Department of Biochemistry, Josef Stefan Institute, Ljubljana, Slovenia.
J Periodontol. 1993 May;64(5 Suppl):485-91.
Cellular and molecular events during the development of inflammatory disease are accompanied by the release of host lysosomal cysteine proteinases (CPs) affecting not only degradation of matrix proteins but possibly also antigen processing and chemotaxis of neutrophils. Activity measurements of Cat B and Cat L could not be used as an accurate indicator of disease activity in individual patients, although average values were higher in patients with more advanced periodontal inflammation. In contrast, simultaneous decrease of cystatin C and alpha 2-macroglobulin (alpha 2-M) in inflamed gingiva and gingival fluid, respectively, might be useful diagnostic/prognostic factors. While the total and the free form of alpha 2-M in gingival fluid decreased with the progression of the disease, the complexed alpha 2-M form was hardly detectable. This indicates an increased consumption of this inhibitor by various proteinases and clearance of protease: alpha 2-M complexes by macrophages. Elevated serum levels of alpha 2-M were found in patients with more pronounced disease, suggesting a systemic host response. In addition, high levels of stefin A and moderate levels of kininogen were observed in gingival tissue homogenates. Stefin A was also found to play a role in the inhibition of neutrophil chemotaxis. In addition, other proteinases which are released at inflammatory sites from neutrophils, macrophages, lymphocytes, and/or bacteria may degrade the cystatins, thereby further increasing CP activities. Increased CP activity may inactivate serine protease inhibitors, leading to the so-called "proteolytic burst."
炎症性疾病发展过程中的细胞和分子事件伴随着宿主溶酶体半胱氨酸蛋白酶（CPs）的释放，这不仅影响基质蛋白的降解，还可能影响抗原加工和中性粒细胞的趋化作用。尽管在牙周炎更严重的患者中组织蛋白酶B（Cat B）和组织蛋白酶L（Cat L）的活性测量平均值较高，但不能将其用作个体患者疾病活动的准确指标。相比之下，炎症牙龈组织和龈沟液中半胱氨酸蛋白酶抑制剂C（cystatin C）和α2-巨球蛋白（α2-M）分别同时降低，可能是有用的诊断/预后因素。随着疾病进展，龈沟液中α2-M的总量和游离形式减少，而复合形式的α2-M几乎检测不到。这表明各种蛋白酶对这种抑制剂的消耗增加，以及巨噬细胞对蛋白酶-α2-M复合物的清除。在病情更严重的患者中发现血清α2-M水平升高，提示存在全身宿主反应。此外，在牙龈组织匀浆中观察到高水平的丝氨酸蛋白酶抑制剂A（stefin A）和中等水平的激肽原。还发现stefin A在抑制中性粒细胞趋化作用中发挥作用。此外，在炎症部位从中性粒细胞、巨噬细胞、淋巴细胞和/或细菌释放的其他蛋白酶可能会降解半胱氨酸蛋白酶抑制剂，从而进一步增加CP的活性。CP活性增加可能会使丝氨酸蛋白酶抑制剂失活，导致所谓的“蛋白水解爆发”。
