[Granzyme B: an essential protease for the inflammatory response]

Granzyme B is a serine protease produced by cytotoxic lymphocytes and capable of inducing rapid target cell death by apoptosis. This effect was found to be closely correlated with the presence of perforin, or pore-forming protein, also contained in the cytoplasmic granules of cytotoxic lymphocytes. Subsequent data suggested that the chief role of perforin is to facilitate accessibility of granzyme B to its cytoplasmic and nuclear targets. Granzyme B may penetrate within the cytoplasm autonomously via a membrane receptor expressed by the target cell, before entering endocytic vesicles containing the protein. Granzyme B can induce target cell death via two complementary pathways, a cytosolic pathway involving cascade activation of proapoptotic caspases, and a nuclear pathway probably involving a cell cycle regulating protein and/or kinase Cdc2 activation. Recent data have established that non-lymphoid cells, including human epithelial cells, can express granzyme B and release it into the extracellular space during the repair process following disruption of the epidermal barrier. This results in local anti-infectious activity that compensates for the break in the mechanical skin barrier and may be a component of natural immunity.