A novel proinflammatory role for granzyme A

Granzymes are a family of homologous serine proteases involved in inducing apoptosis in virus-infected cells and tumor cells.1, 2 In humans, five granzymes (GrA, GrB, GrH, GrK, and GrM) are expressed, and stored in granules of natural killer (NK) cells, NK-T cells, cytotoxic T cells, and γδ T cells, which are collectively referred to as cytotoxic lymphocytes.1, 2 After release of the granule content in the immunological synapse between a target cell and a cytotoxic lymphocyte, granzymes enter the cytosol of the target cell with the aid of pore-forming protein perforin. Inside the target cell, granzymes cleave various death substrates.1, 2 Macrophages, mast cells, and dendritic cells can also express granzymes but not perforin, suggesting perforin-independent (extracellular) roles of granzymes.3