Kummer J A, Tak P P, Brinkman B M, van Tilborg A A, Kamp A M, Verweij C L, Daha M R, Meinders A E, Hack C E, Breedveld F C
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
Clin Immunol Immunopathol. 1994 Oct;73(1):88-95. doi: 10.1006/clin.1994.1173.
Granzymes A and B are serine proteinases which are stored in the granules of activated cytotoxic T cells and NK cells. Expression of these granzymes by cytotoxic cells in tissues can be used as an activation marker for these cells. To investigate a possible role of cytotoxic lymphocytes in rheumatoid arthritis (RA) and osteoarthritis (OA), we assessed the expression of granzymes A and B by cytotoxic lymphocytes in synovial biopsies from five RA and five OA patients using mAb specific for these serine proteinases. In three of the five RA patients but also in two of the five OA patients granzyme A- and B-expressing lymphocytes were observed in the synovium. Double-labeling immunohistochemical techniques revealed that up to 75% of the granzyme-positive synovial lymphocytes had the CD16+ or CD56+ natural killer cell phenotype. Less than 5% were CD3+, CD8+ cytotoxic T cells, whereas in some patients the phenotype of up to 50% of these cells could not be identified. The presence of granzymes A and B in the synovium of both RA as well as OA patients was confirmed on the molecular level in a second group of 11 RA and 5 OA patients using the polymerase chain reaction. Thus, expression of granzymes A and B occurs in the synovium in patients with RA as well as those with OA. These proteins are mainly expressed by NK cells that may therefore play a role in the pathogenesis of these diseases.
颗粒酶A和颗粒酶B是丝氨酸蛋白酶，储存于活化的细胞毒性T细胞和自然杀伤（NK）细胞的颗粒中。细胞毒性细胞在组织中表达这些颗粒酶可作为这些细胞的活化标志物。为了研究细胞毒性淋巴细胞在类风湿关节炎（RA）和骨关节炎（OA）中可能发挥的作用，我们使用针对这些丝氨酸蛋白酶的单克隆抗体，评估了5例RA患者和5例OA患者滑膜活检组织中细胞毒性淋巴细胞的颗粒酶A和颗粒酶B表达情况。在5例RA患者中的3例以及5例OA患者中的2例滑膜中，观察到了表达颗粒酶A和颗粒酶B的淋巴细胞。双标记免疫组化技术显示，高达75%的颗粒酶阳性滑膜淋巴细胞具有CD16+或CD56+自然杀伤细胞表型。少于5%为CD3+、CD8+细胞毒性T细胞，而在一些患者中，高达50%的这些细胞的表型无法确定。在另一组11例RA患者和5例OA患者中，利用聚合酶链反应在分子水平上证实了RA和OA患者滑膜中存在颗粒酶A和颗粒酶B。因此，颗粒酶A和颗粒酶B在RA患者以及OA患者的滑膜中均有表达。这些蛋白主要由NK细胞表达，因此可能在这些疾病的发病机制中发挥作用。
