Human mast cells produce and release the cytotoxic lymphocyte associated protease granzyme B upon activation

Death by a Thousand Cuts: Granzyme Pathways of Programmed Cell Death

“…There are comparable levels of GzmB transcripts in resting and activated human pDC, but significantly higher levels of GzmB protein in activated cells (6). Human mast cells upon activation express higher levels of GzmB mRNA than are found in CTL, but the corresponding protein levels are considerably lower in mast cells (7). Mouse memory CTLs express abundant GzmB mRNA but no protein (50).…”

“…It is unclear whether, during killer cell degranulation, the immune synapse forms a perfectly tight gasket that completely prevents granzymes from leaking out into the extracellular space. Moreover, increasing evidence suggests that granzymes may be expressed without perforin and secreted by other types of white blood cells during inflammation, including mast cells, neutrophils, activated macrophages, as well as potentially some nonhematopoietic cells, such as UV-damaged keratinocytes (7,10,11,(176)(177)(178). GzmB is even expressed by developing germ cells in the testes and by syncytial trophoblasts in the placenta (14).…”

“…GzmB is also expressed in both normal and neoplastic human mast cells in vitro and in vivo (7). GzmB localizes to specific granules in human mast cells and is secreted upon activation as it is in CTL.…”

Granzymes in cancer and immunity

“…For example, transformed and activated primary B cells, mast cells, keratinocytes, basophils, macrophages and blood polymorphonuclear neutrophils have all been shown to express granzyme B. 11,[14][15][16][17][18][19][20] Mast cells are especially abundant at the boundary between the internal environment and the outside world, for example, in the skin and lungs, and are thus perfectly situated to coordinate an immune response against a nascent infection. Granzyme B, but not granzyme A or perforin, is expressed by mast cells and secreted in an active form after ligation of the FceR1 receptor.…”

“…Coupled with observations that certain granzymes are expressed and secreted by B cells, mast cells, keratinocytes, basophils, as well as other cell types, in the absence of detectable perforin, this suggests that granzymes may have hitherto unsuspected roles in immunity. 11,[14][15][16][17][18][19][20] Thus, in addition to acting as cell death effector molecules on delivery to target cells, granzymes may also possess activity on release into the extracellular space ( Figure 1). The expanding role for granzymes as possible soluble mediators of inflammation will be discussed later in this review.…”