Spaeny-Dekking E H, Hanna W L, Wolbink A M, Wever P C, Kummer J A, Swaak A J, Middeldorp J M, Huisman H G, Froelich C J, Hack C E
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
J Immunol. 1998 Apr 1;160(7):3610-6.
Activated CTLs and NK cells induce apoptosis via multiple mechanisms, including that termed granule exocytosis. The latter pathway consists of vectorial secretion of perforin and a family of granule-associated serine proteases (granzymes) to the target cell. To establish whether granzymes are released extracellularly during cytolytic reactions in vivo, ELISAs that measure the native enzymes were developed and were found to specifically detect granzyme A (GrA) and granzyme B (GrB) at picogram concentrations. Low levels of GrA and GrB were present in plasma of healthy individuals (GrA, 33.5 pg/ml (median); GrB, 11.5 pg/ml (median)), whereas significantly higher levels were present in patients with ongoing CTL response, i.e., patients suffering from infections by EBV or HIV type 1. Markedly elevated levels were also noted in synovial fluid of patients with active rheumatoid arthritis. The measurement of soluble granzymes should be useful to assess clinical disorders associated with activated CTL and NK cells. Furthermore, these results suggest that granzymes mediate biologic effects beyond their described role in apoptotic cell death.
活化的细胞毒性T淋巴细胞（CTL）和自然杀伤细胞（NK细胞）通过多种机制诱导细胞凋亡，包括颗粒胞吐作用。后一种途径包括将穿孔素和一组颗粒相关丝氨酸蛋白酶（颗粒酶）向靶细胞进行定向分泌。为了确定在体内溶细胞反应过程中颗粒酶是否会释放到细胞外，人们开发了用于检测天然酶的酶联免疫吸附测定（ELISA），并发现其能够特异性地检测皮克浓度的颗粒酶A（GrA）和颗粒酶B（GrB）。健康个体血浆中存在低水平的GrA和GrB（GrA，33.5皮克/毫升（中位数）；GrB，11.5皮克/毫升（中位数）），而在有持续CTL反应的患者中，即感染EB病毒或1型人类免疫缺陷病毒的患者中，其水平明显更高。在活动性类风湿关节炎患者的滑液中也观察到显著升高的水平。可溶性颗粒酶的检测对于评估与活化的CTL和NK细胞相关的临床疾病应该是有用的。此外，这些结果表明颗粒酶介导的生物学效应超出了其在凋亡性细胞死亡中所描述的作用。
