Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0042109 (
urticaria
)
6,569
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 Kit
W-sh/W-sh
mice. Prior local reconstitution of Kit
W-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.
...
PMID:Mast cells are critical for the limitation of thrombin-induced skin inflammation. 2878 94
