Figure 2.

Intracellular and putative extracellular functions of Granzyme A. Classically GrA and other granzymes have been described as promoting cytotoxic lymphocyte mediated eradication of target cells via the induction of (apoptotic) cell death. Upon recognition of the target cell CTL release granule content into the immunological synapse, perforin provides access to the cytosol and granzymes promote cell death intracellularly (1). During a number of inflammatory disease statues GrA accumulates in extracellular space and is suggested to (i) induce release of pro-inflammatory cytokines in fibroblasts, epithelial cells, monocytes, and macrophages (3, 85, 86), (ii) remodel extracellular matrix (87–91), (iii) contribute to the migration of activated CTLs through tissue and extravasation of these cells from the vasculature (88), and (iv) cleavage of (cell surface) receptors as the Thrombin like receptor in neurite retraction (92–94).