Granzyme B, a key protease in the inflammatory response

Granzyme B is a serine protease produced by cytotoxic lymphocytes and capab le of inducing rapid target cell death by apoptosis. This effect was found to be closely correlated with the presence of perforin, or pore-forming pro tein, 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. Granzym e B may penetrate within the cytoplasm autonomously via a membrane receptor expressed by the target cell, before entering endocytic vesicles containin g the protein. Granzyme B can induce target cell death via two complementar y pathways, a cytosolic pathway involving cascade activation of proapoptoti c caspases, and a nuclear pathway probably involving a cell cycle regulatin g 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 fol lowing disruption of the epidermal barrier. This results in local anti-infe ctious activity that compensates for the break in the mechanical skin barri er and may be a component of natural immunity.