ROLE OF THE GRANZYME B INHIBITOR PI-9 IN LYMPHOCYTES AND ANTIGEN-PRESENTING CELLS

C.F.Classen, and K.-M.Debatin. University Children's Hospital Ulm, Prittwitzstr.43, D-89070 Ulm, Germany

e-mail: carl.classen@medizin.uni-ulm.de

Killer cells induce apotosis in their targets by CD95 ligand and by granular enzymes, especially granzyme B (GrzB). Proteinase Inhibitor 9 (PI-9) - a cytosolic serine protease inhibitor (serpin) - is the only known natural antagonist of GrzB. Using PI-9 transfected cells of the neuroblastoma cell line SH-EP, we found significant decrease of GrzB induced apoptosis compared to vector controls. In vivo, PI-9 is mainly expressed in cytotoxic lymphocytes and in antigen presenting cells. Its proposed function is protection of cytotoxic or antigen-presenting cells from cross-fire at areas of inflammation. It has also been shown to influence activation-induced death in NK cells. Therefore, PI-9 might be a relevant factor in immune regulation.

We studied PI-9 expression in lymphocytes and monocytes upon in-vitro stimulation by lipopolysaccharides and a number of cytokines. Our preliminary data indicate that PI-9 expression is correlated with the activation status of the monocyte/macrophage system. It might play a significant role in the pathogenesis of disorders like autoimmunity or lymphohistiocytosis.