Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic urticaria (CU), defined as recurrence of wheals with or without angioedema for more than 6 weeks, is a quite common disease that may severely worsen the quality of life. Studies carried out during the last 2 decades have demonstrated an autoimmune pathogenesis mediated by functionally active autoantibodies to the high affinity IgE receptor (FcepsilonRI) or to IgE which are able to induce histamine release from basophils and mast cells. However, such mechanism can be detected in less than 50% of patients only. The present article reviews recent findings showing an additional pathogenic mechanisms in CU patients: activation of the coagulation cascade resulting in thrombin production. Thrombin is a serine protease which may play a key role in urticaria, being able to induce edema through an increase in vascular permeability, mast cell activation and degranulation, and to induce the production of the anaphylotoxin C5a. Such mechanism seems to be active in the majority of CU patients, however their relationship with anti-FcepsilonRI or anti-IgE autoantibodies is still matter of research.
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PMID:Chronic urticaria: a disease at a crossroad between autoimmunity and coagulation. 1796 29

Thrombin, a key player in coagulation, is widely held to induce and promote inflammation. As of now, the features, kinetics and control of thrombin's proinflammatory effects on the skin remain to be characterized in detail. We, therefore, injected thrombin into the ear skin of mice and observed strong, dose-dependent and transient ear swelling responses as well as mast cell (MC) degranulation. Unexpectedly, thrombin induced even stronger, not reduced, ear swelling in MC-deficient KitW-sh/W-sh mice. Prior local reconstitution of KitW-sh/W-sh mice with MCs inhibited this effect, indicating that MCs may contribute to the control of thrombin-induced skin inflammation. In line with previous studies, we found that MCs express the thrombin receptors PAR1, PAR3 and PAR4, thrombin induces direct and dose-dependent MC degranulation, and that degranulated MCs inactivate thrombin. Further findings suggested that MC-mediated protection from thrombin-induced inflammation is likely to rely on the effects of MC proteases. We show for the first time that MC-deficient mice and MC protease 4-deficient mice with normal numbers of MCs show markedly increased ear swelling in response to thrombin as compared to wild-type mice. Taken together, these results suggest that thrombin-induced skin inflammation is controlled, in part, by MC protease 4 released from activated MCs. For MC-driven diseases such as chronic spontaneous urticaria, which has been linked to increased thrombin generation, this might mean that MCs may contribute to the resolution of skin inflammatory responses.
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PMID:Mast cells are critical for the limitation of thrombin-induced skin inflammation. 2878 94