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In response to cell injury, caused, for example, by trauma, several processes must be initiated simultaneously to achieve an acute inflammatory response designed to prevent sustained tissue damage and infection and to restore and maintain tissue homeostasis. Detecting cell injury is facilitated by the fact that damaged cells release intracellular molecules(More)
Mast cells have been attributed several functions in both health and disease. Mast cell activation and release of inflammatory mediators are associated with the pathogenesis of several diseases, in particular that of allergic diseases. While the notion of mast cells as important, protective sentinel cells is old, this feature of the cell is not well(More)
The human chymase (HC) is a major granule constituent of mast cells (MCs) residing in the connective tissue and the sub-mucosa. Although many potential substrates have been described for this important MC enzyme, its full range of in vivo substrates has most likely not yet been identified. A major step toward a better understanding of the function of the HC(More)
Four hematopoietic serine proteases are common to the mast cell chymase locus of all analyzed mammals: α-chymase, cathepsin G, granzyme B, and granzyme C/H. Apart from these common genes, the mouse and rat loci hold additional granzyme-, β-chymase-, and Mcpt8-like genes. To better understand the functional consequences of these additional enzymes and to be(More)
Mast cells are well known for their role in allergic inflammation where, upon aggregation of the high-affinity immunoglobulin E receptor, they release mediators such as histamine that cause classical allergic symptoms. Mast cells are located in almost all tissues and are especially numerous in organs that interface with the environment. Given this strategic(More)
Mast cells are among the first cells of our immune system to encounter exogenous danger. Intracellular receptors such as nucleotide-binding oligomerization domain (Nod) play an important role in responding to invading pathogens. Here, we have investigated the response of human mast cells to the Nod1 ligand M-TriDAP. Human cord blood-derived mast cells(More)
ViscoGel, a chitosan-based hydrogel, has earlier been shown to improve humoral and cell-mediated immune responses in mice. In this study, a Phase I/IIa clinical trial was conducted to primarily evaluate safety and secondarily to study the effects of ViscoGel in combination with a model vaccine, Act-HIB to Haemophilus influenzae type b, administered as a(More)
IL-33 is a recently discovered cytokine involved in induction of Th2 responses and functions as an alarmin. Despite numerous recent studies targeting IL-33, its role in vivo is incompletely understood. Here we investigated inflammatory responses to intraperitoneal IL-33 injections in wild-type and mast cell-deficient mice. We found that wild-type mice, but(More)
Serine proteases are major granule constituents of mast cells, neutrophils, T cells and NK cells. The genes encoding these proteases are arranged in different loci. The mast cell chymase locus e.g. comprises at least one alpha-chymase, one cathepsin G, and two granzyme genes in almost all mammalian species investigated. However, in the gray, short-tailed(More)
Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The(More)