Activation of mast cells induced by agonists of proteinase-activated receptors under normal conditions and during acute inflammation in rats

Dugina, T. N.; Ev, Kiseleva; Glusa, Erika; Strukova, S. M.

doi:10.1016/s0014-2999(03)01752-7

Cited by 29 publications

(24 citation statements)

References 36 publications

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“…Studies on animal models have shown that thrombin can induce MC degranulation with a potency similar to that of FceRI-mediated activation (32). In a rat model, Dugina et al (33) , which promotes the release of histamine (33). MC express PAR-1 and PAR-2.…”

Section: Role Of Eosinophils Tissue Factor and Thrombinmentioning

confidence: 99%

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Tedeschi

Kolkhir

Asero³

et al. 2014

Allergy

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Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1-antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.Chronic urticaria (CU) is a widespread skin disease characterized by the recurrence of transient wheals and itch for more than 6 weeks. It is believed that over 50% of CU cases are accompanied by a deep subcutaneous and/or submucosal edema, called angioedema (AE; 1).It is well known that the characteristic symptoms of urticaria appear following the activation of mast cells (MCs) and basophils in the skin by various stimuli. These cells release several biologically active substances, the most important of which is histamine. Histamine induces vasodilation, increases vascular permeability and stimulates sensory nerve endings. These effects lead to the appearance of erythema, wheals and itch (2). It is supposed that other biologically active substances may have similar effects. These include serotonin, C3a and C5a anaphylatoxins, platelet-activating factor (PAF), neuropeptides, and arachidonic acid metabolites (prostaglandin D2, leukotrienes C4, D4 and E4; 3).Activation and degranulation of basophils and MCs may occur by immunological (formation of immune complexes, complement activation, IgE cross-linking), nonimmunological (pseudoallergy, infection, or direct effect of agents on MCs), or mixed mechanisms. The mechanism and cause of urticaria remain unclear in many patients with CU.In recent years, attention was paid to several important aspects of the disease pathogenesis. It is believed that about 30-50% of patients have CU symptoms associated with autoimmune reactions and synthesis of autoantibodies against IgE (4) and/or the FceRI a-subunit on MCs and basophils (autoimmune/autoreactive urticaria; 5). Furthermore, these patients show an increased frequency of HLA DRB1*04 (DR4) as it occurs in other autoimmune diseases (6). The role of coagulation casc...

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Section: Role Of Eosinophils Tissue Factor and Thrombinmentioning

confidence: 99%

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Tedeschi

Kolkhir

Asero³

et al. 2014

Allergy

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“…trypsin, chymotrypsin, thrombin) directly induce MC activation [20,72]. Serine proteases have been known to be important regulators of many biological functions, such as hemostasis, fibrinolysis, tissue repair, and the digestion of dietary protein.…”

Section: Ige−independent MC Activationmentioning

confidence: 99%

Intracellular signaling pathways in IgE-dependent mast cell activation

Kopeć

Panaszek

Wandalsen

2006

Arch. Immunol. Ther. Exp.

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Mast cells (MCs) are both central effectors and signaling cells in allergic reactions. Their key role in the immunopathology of asthma and other allergic diseases has been well documented. Molecular events leading to MC activation have not been yet fully established, however. Recent studies emphasize the key role of the protein tyrosine kinases Lyn and Fyn in MC signal transduction. The finding that Lyn kinase negatively regulates MC degranulation and that Fyn kinase enhances this effector response is of great importance. This creates new possibilities for therapeutic intervention in asthma and other allergic diseases. This review summarizes current knowledge on MC intracellular signaling and discusses the most recent strategies for the treatment of allergic diseases based on MC signaling pathway inhibition.

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“…Vascular permeability sharply increased 30 min after the start of the study (by 2 times), which is typical of the exudation stage [4].…”

Section: Resultsmentioning

confidence: 84%

“…PAR-expressing mast cells are also involved in the inflammatory process [3]. Our studies showed that the response of peritoneal mast cells (PMC) to thrombin increases in rats with experimental acute peritonitis, which reflects activation of PAR1 expression under these conditions [4] and suggests generation of thrombin and other proteinases of the blood coagulation system in the inflammatory focus. Thrombin converts blood protein C into APC.…”

Section: Abstract: Mast Cells; Inflammation; Activated Protein C; Thmentioning

confidence: 73%

Effect of activated protein C on secretory activity of rat peritoneal mast cells

et al. 2006

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Generation of thrombin and activated protein C in the inflammatory focus was demonstrated in rats with experimental acute peritonitis. The contents of thrombin and activated protein C peaked by the 30th and 120th minute of inflammation, respectively. In vitro study showed a decrease in spontaneous and compound 48/80-induced secretion of beta-hexosaminidase by peritoneal mast cells under the influence of activated protein C in low concentrations. The antiinflammatory effect of protein C in the focus of acute peritonitis is probably realized through NO release from peritoneal mast cells. This conclusion is derived from the data that L-NAME abolishes the protective effect of activated protein C.

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Activation of mast cells induced by agonists of proteinase-activated receptors under normal conditions and during acute inflammation in rats

Cited by 29 publications

References 36 publications

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Intracellular signaling pathways in IgE-dependent mast cell activation

Effect of activated protein C on secretory activity of rat peritoneal mast cells

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