Mast cells in innate immunity

Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin

“…Mast cells are known to seed in close proximity to EC of blood vessels 30 and may directly act on EC and SMC, via secreted factors, including pro-inflammatory cytokines and chemokines. [30][31][32] The observation that BMMC secrete gzmB and that rgzmB induces disintegration of EC-cell-cell contacts at concentrations where gross morphological changes and EC detachment are not yet observed (3 mg/ml), may indicate that mast cell-derived gzmB contributes to the recruitment of leukocytes by facilitating their transendothelial migration.…”

“…[30][31][32] The observation that BMMC secrete gzmB and that rgzmB induces disintegration of EC-cell-cell contacts at concentrations where gross morphological changes and EC detachment are not yet observed (3 mg/ml), may indicate that mast cell-derived gzmB contributes to the recruitment of leukocytes by facilitating their transendothelial migration. 33 Evidence that intraperitoneal administration of mMCP-6 results in neutrophil infiltration into the peritoneum 27 supports the idea of a general role for mast cell-derived proteases in leukocyte recruitment.…”

“…Mast cells have been implicated in the control of bacterial and viral infections, 31,32 immunosurveillance, in disease progression 1,3,30 and, more recently, as intermediaries in regulatory T cell tolerance. 40 However, the role gzmB may play in any of these processes is unknown.…”

“…Mast cell migration and accumulation at sites of viral infections supports this contention. 30 The presence of mast cells and gzmB-positive cells at the invasive front of the synovium and elevated levels of gzmB in serum and synovial fluids is a hallmark of patients with active Figure 5 rgzmB induces cell death in fibroblasts via cell detachment. (a, b) MEFs were plated before treatment (triplicates) with the indicated amounts of rgzmB or progzmB in the absence or presence of a sublytic dose of SLO (0.5 mg/ml) for 4 h or were left untreated (medium).…”

The role and regulation of 11β-hydroxysteroid dehydrogenase type 1 in the inflammatory response

“…They reside in tissues, usually at epithelial surfaces and around blood vessels and nerves where they act as sentinels to guard against certain bacteria and parasites and where they play a key role in repair processes by promoting angiogenesis and fibrosis (reviewed in Marshall and Jawdat, 2004;Nigrovic and Lee, 2005;Woolley, 2003)). Mast cells are ideally placed at the pinnacle of an inflammatory cell cascade to shape and direct the subsequent immune response.…”