Human mast cell tryptase: a stimulus of microvascular leakage and mast cell activation

He, Shaoheng; Walls, Andrew F.

doi:10.1016/s0014-2999(97)83033-6

Cited by 151 publications

(88 citation statements)

References 49 publications

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“…This is what would be expected in IgE-mediated anaphylaxis. One had a serum tryptase concentration of 62.9 lg.l ) at 3 h. Tryptase is one of the many mediators present in mast cell granules and released in anaphylaxis, and has been shown to cause mast cell degranulation, histamine release and increased microvascular permeability [17,21]. It would have been much more impressive if these patients had recorded a surprisingly low serum tryptase level due to altered mast cell release caused by sugammadex.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is ample evidence that once mast cells are activated by an allergen, allergen-independent mechanisms are, at least in part, responsible for the propagation and amplification of the type-1 hypersensitivity reaction (e.g. tryptase, neuropeptides, sphingosine-1-phosphate, platelet activating factor, anaphylatoxins and the mast cell-leucocyte-cytokine cascade have all been shown to activate mast cells) [15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model*

Clarke¹,

Sadleir²,

Platt³

2012

Anaesthesia

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SummaryThe availability of sugammadex as a selective encapsulating agent for rocuronium has led to speculation that it may be useful in mitigating rocuronium-induced anaphylaxis. Off-label use of sugammadex for this indication has already been documented in case reports although there are theoretical objections to the likelihood of an allergen-binding agent's being able to attenuate the immunological cascade of anaphylaxis. Using a cutaneous model of anaphylaxis in rocuronium-sensitised patients, we were unable to demonstrate that sugammadex was effective in attenuating the type-1 hypersensitivity reaction after it has been triggered by rocuronium, but we were able to demonstrate that these patients are anergic to sugammadex-bound rocuronium. These findings demonstrate that a cyclodextrin can bind an allergen and exclude it from interacting with the immune system, and may potentially lead to novel applications in other allergic diseases. However, there is no evidence that sugammadex should be used for the treatment of rocuronium-induced anaphylaxis, and clinical management should follow established protocols. Accepted: 23 October 2011In many countries neuromuscular blocking drugs are the most common agents responsible for anaphylaxis during general anaesthesia, with rocuronium being one of the most frequently implicated [1,2]. One of the basic principles in the management of anaphylaxis is the removal of the triggering agent [3]. However, although there is evidence that the removal of an allergen from its corresponding cell-bound-specific antibody will attenuate the process of mediator release from the mast cell in vitro [4], there is no evidence that it will alter the clinical course of anaphylaxis in vivo.Sugammadex is a modified c-cyclodextrin with a hydrophobic cavity designed to encapsulate rocuronium and other steroid-based neuromuscular blocking drugs [5]. Intermolecular (van der Waals) forces result in a water-soluble complex with a high association rate. When used for the reversal of rocuronium-induced neuromuscular blockade, sugammadex is very effective [6]. Sugammadex is rapidly distributed to the effect compartment [7], its affinity for rocuronium is greater than that of the nicotinic acetylcholine receptor [8], and the influence of rocuronium at the nicotinic acetylcholine receptor is both reversible and relatively insensitive [9]. Consequently, sugammadex has been shown to reverse profound rocuronium-induced neuromuscular blockade within minutes [6].

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model*

Clarke¹,

Sadleir²,

Platt³

2012

Anaesthesia

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“…It is stored almost exclusively in the secretory granules of mast cells (34). Tryptase acts to induce microvascular leakage (35), the chemotaxis of inflammatory cells (36), and stimulates the release of IL-6 and -8 through the MAPK / AP-1 pathway (37). It has been reported that tryptase secretion is significantly increased in the colonic tissue of ulcerative colitis (UC) patients (38) and that the intracolonic administration of PAR 2 agonists such as tryptase and trypsin induced an inflammatory reaction characterized by granulocyte infiltration, increased wall thickness, tissue damage, and elevated T-helper cell type 1 cytokine (39,40).…”

Section: Anti-proteinase / Par 2 Therapy In Colonic Mucosal Inflammationmentioning

confidence: 99%

Basic and Translational Research on Proteinase-Activated Receptors: Implication of Proteinase/Proteinase-Activated Receptor in Gastrointestinal Inflammation

Yoshida

Yoshikawa

2008

J Pharmacol Sci

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Abstract. Recently, the role of serine proteinases in the pathogenesis of inflammation and autoimmune diseases via interaction with the proteinase-activated receptor (PAR) has attracted attention. Activation of PAR has a pro-inflammatory effect through the overproduction of inflammatory cytokines such as interleukin (IL)-6 and IL-8. PAR 2 activation in human esophageal epithelial cells by trypsin induces NFκB-and AP-1-dependent IL-8 production in association with activation of p38 MAPK and ERK1 / 2, suggesting that esophageal inflammation may be induced by PAR 2 activation via reflux of trypsin. It has been also proposed that Helicobacter pylori (H. pylori) induces PAR expression in the gastric epithelial cells and H. pylori-derived serine proteinase promotes IL-8 production via PAR in the epithelial cells. In addition, an increase of PAR-dependent IL-8 production has been observed in H. pylori-infected human gastric mucosa, suggesting an important role for PAR 2 in the modulation of gastric inflammation associated with H. pylori. Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. We demonstrated that anti-tryptase therapy may become a new therapeutic strategy in human ulcerative colitis. Thus, the role of PAR in the gastrointestinal tract has been gradually clarified, but further investigations are needed because the receptor has a variety of functions.

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“…or intraluminally cause increased airway resistance in the guinea pig by releasing tachykinins from sensory nerves (9). Tryptase also contracts human bronchi (10), induces plasma extravasation (14), infiltration of neutrophils and eosinophils (15), release of cytokines and expression of adhesion molecules (16), and stimulates proliferation of smooth muscle (17,18) and fibroblasts (19,20). These inflammatory effects of tryptase may be mediated by PAR2.…”

Section: Protease-activated Receptor 2 Mediates Eosinophil Infiltratimentioning

confidence: 99%

Protease-Activated Receptor 2 Mediates Eosinophil Infiltration and Hyperreactivity in Allergic Inflammation of the Airway

Schmidlin

Amadesi

Dabbagh³

et al. 2002

The Journal of Immunology

305

260

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Trypsin and mast cell tryptase can signal to epithelial cells, myocytes, and nerve fibers of the respiratory tract by cleaving proteinase-activated receptor 2 (PAR2). Since tryptase inhibitors are under development to treat asthma, a precise understanding of the contribution of PAR2 to airway inflammation is required. We examined the role of PAR2 in allergic inflammation of the airway by comparing OVA-sensitized and -challenged mice lacking or overexpressing PAR2. In wild-type mice, immunoreactive PAR2 was detected in airway epithelial cells and myocytes, and intranasal administration of a PAR2 agonist stimulated macrophage infiltration into bronchoalveolar lavage fluid. OVA challenge of immunized wild-type mice stimulated infiltration of leukocytes into bronchoalveolar lavage and induced airway hyperreactivity to inhaled methacholine. Compared with wild-type animals, eosinophil infiltration was inhibited by 73% in mice lacking PAR2 and increased by 88% in mice overexpressing PAR2. Similarly, compared with wild-type animals, airway hyperreactivity to inhaled methacholine (40 μg/ml) was diminished 38% in mice lacking PAR2 and increased by 52% in mice overexpressing PAR2. PAR2 deletion also reduced IgE levels to OVA sensitization by 4-fold compared with those of wild-type animals. Thus, PAR2 contributes to the development of immunity and to allergic inflammation of the airway. Our results support the proposal that tryptase inhibitors and PAR2 antagonists may be useful therapies for inflammatory airway disease.

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Human mast cell tryptase: a stimulus of microvascular leakage and mast cell activation

Cited by 151 publications

References 49 publications

The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model*

The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model*

Basic and Translational Research on Proteinase-Activated Receptors: Implication of Proteinase/Proteinase-Activated Receptor in Gastrointestinal Inflammation

Protease-Activated Receptor 2 Mediates Eosinophil Infiltration and Hyperreactivity in Allergic Inflammation of the Airway

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