Abstracts (complete list) - Wissenschaft Online

Praxedis Martin, Julian Pardo, Reinhard Wallich, Klaus Ebnet, Sandra Iden, Aynur
Ekiciler, Arno Muellbacher, Michael Huber, Markus M. Simon
Granzyme B is expressed in mouse mast cells in vivo and in
vitro and causes delayed cell death independent of perforin
The proteases granzyme (gzm) A and gzmB have been mainly linked to natural killer
(NK) cells and cytotoxic T lymphocytes (CTL) and their lytic machinery so far. Together
with perforin (perf) both gzms are released through exocytosis of NK/CTL secretory
granule contents into a synapse formed between the killer cell and its target cell. After
their access to the target cell cytosol they initiate alternative, but strictly perfdependent
proteolytic pathways leading to apoptosis. However, in addition to these
intracellular activities, secreted gzmA and gzmB may also function extracellularly by
cleaving components of extracellular matrices and basal laminae, including fibronectin
and vitronectin. These processes may result in cell detachment of susceptible targets
and indirectly in their delayed death, termed anoikis. Recent evidence suggests that
cells other than NK cells and CTL also express gzms, indicating their involvement in
additional biological activities.
Here we present evidence that skin-, but not lung-associated primary mouse mast cells
as well as in vitro differentiated bone marrow derived mast cells (BMMC) express gzmB,
but not gzmA or perf. GzmB is associated with cytoplasmic granules of mouse mast cells
and secreted by BMMC upon Fcε-receptor mediated activation. BMMC from wild type but
not gzmB-deficient mice cause cell death in susceptible adherent target cells indicating
that the perf-independent cytotoxic potential of BMMC is executed by gzmB.
Furthermore, purified recombinant gzmB induces a disorganization of endothelial cellcell
contacts. The data suggest that activated mast cells contribute via secreted gzmB to
cell death, increased vascular permeability, leukocyte extravasation and subsequent
inflammatory processes in affected tissues.