Human Granzyme A Antibody from BIOLEGEND

Granzyme A is a serine protease belonging to the granzyme family and is expressed exclusively by cytotoxic T cells (CTL) and NK cells. Most circulating CD56+CD8- NK cells, and approximately half of circulating CD8+ T cells, coexpress both granzymes A and B. In contrast, few circulating CD4+ T cells express granzyme A or B. Activation of CD8+ and CD4+ T lymphocytes induces substantial expression of granzyme B, but not granzyme A. Following receptor-mediated conjugate formation between a granzyme-containing cell and an infected or transformed target cell, granzymes enter the target cell via endocytosis and induce apoptosis. Granzyme A was found to induce caspase-independent cell death when it enters into the target cell by perforin. Once in a cell, granzyme A activates DNA nicking by DNAse NM23-H1, a tumor suppressor gene product whose expression is reduced in transformed, metastatic cells. Dysregulation of this pathway results in several human diseases, such as hemophagocytic lymphohistiocytosis. Besides the protease activity, granzyme A induces human lung fibroblasts to produce IL-6 and IL-8. Cytokine induction is abrogated by treating the serine protease with the suicide serine protease inhibitor 3,4-dichloroisocoumarin. Other fibroblast lines, as well as epithelial cells, produce cytokines in response to granzyme A. These findings suggest that granzyme A can function as an activation molecule with potentially important immunoregulatory functions. However, CTLs from mice lacking granzyme A induce morphologically normal apoptosis in vitro, but those from mice that are deficient of granzyme B induce the nuclear features of apoptosis (particularly DNA fragmentation) more slowly than do wild-type CTLs.