活性化凝固因子は補体活性化を介して皮膚マスト細胞・好塩基球を活性化する

抄録

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by almost daily recurring wheal and flare with itch for more than 6 weeks in association with degranulation of mast cells and/or basophils. However, mechanism of mast cell- and basophil-activation in CSU has been unclear. Recently, the involvement of the extrinsic coagulation pathway triggered by tissue factor (TF) has been suggested in the pathogenesis of CSU. In this study, we investigated if TF-triggered production of activated extrinsic coagulation factors, such as Xa and IIa, directly or indirectly activate human skin mast cells and peripheral basophils. Although Xa and IIa did not activate human skin mast cells and basophils for themselves, complement C5a produced by the activated by Xa and IIa from C5 induced degranulation of mast cells and basophils. Moreover, the reactions were abolished by the treatment with a C5a receptor (C5a) antagonist. Thus, we demonstrated that C5a, but not activated extrinsic coagulation factors, induces degranulation of human skin mast cells and basophils via C5aR. C5aR antagonist could be effective treatment for patients with severe and refractory CSU.