EXTRACELLULAR GRANZYME-A AND GRANZYME-B IN HUMANS - DETECTION OF NATIVE SPECIES DURING CTL RESPONSES IN-VITRO AND IN-VIVO

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 v ivo, ELISAs that measure the native enzymes were developed and were fo und to specifically detect granzyme A (GrA) and granzyme B (GrB) at pi cogram concentrations. Low levels of GrA and GrB were present in plasm a of healthy individuals (GrA, 33.5 pg/ml (median); GrB, 11.5 pg/ml (m edian)), 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 synovi al fluid of patients with active rheumatoid arthritis, The measurement of soluble granzymes should be useful to assess clinical disorders as sociated with activated CTL and NK cells, Furthermore, these results s uggest that granzymes mediate biologic effects beyond their described role in apoptotic cell death.