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- Title
Mast cell chymase degrades fibrinogen and fibrin.
- Authors
Lipitsä, T.; Siiskonen, H.; Naukkarinen, A.; Harvima, I.T.
- Abstract
Summary: Background: The accumulation of immunoreactants and fibrinoid necrosis of postcapillary vessel walls are common pathological features of cutaneous immune complex vasculitis. In more advanced lesions, these immunoreactants are subject to proteolysis. Mast cell chymase is a powerful enzyme that can degrade several substrates including the extracellular matrix. Heparin can influence the catalytic properties of chymase. Objectives: To study the effects of recombinant human (rh) chymase on fibrinogen, coagulation and fibrinolysis, and to relate these effects to the pathogenesis of vasculitis. Methods: The colocalization of chymase and fibrin in vasculitis specimens was analysed by immunohistochemical double staining. Fibrinogen and fibrin were treated with rh‐chymase and the effects were studied in vitro by sodium dodecylsulfate polyacrylamide gel electrophoresis and a variety of clotting and fibrin gel experiments. The effects of rh‐chymase on vasculitis cryosections were analysed by direct immunofluorescence. Results: Chymase‐positive mast cells were associated with fibrin‐positive vessels in vasculitis cryosections. Rh‐chymase degraded the alpha‐, beta‐ and gamma‐chains of fibrinogen, while heparin enhanced the degradation of the beta‐chain. Rh‐chymase pretreatment of fibrinogen prolonged thrombin‐induced clotting time. Fibrinogen degradation products induced by rh‐chymase increased the clotting time of human plasma. Rh‐chymase degraded fibrin gel prepared from fibrinogen or human plasma. Immunofluorescence staining positivity of fibrin in vasculitis cryosections decreased after pretreatment with rh‐chymase for 24 h, and heparin enhanced this effect. Conclusions: Mast cell chymase may constitute a previously unrecognized endogenous anticoagulant and fibrinolytic enzyme, and may be involved in the clearance of fibrin from vessel walls in aged vasculitis lesions. What's already known about this topic? The accumulation of immunoreactants and fibrinoid necrosis of postcapillary vessel walls are common pathological features of cutaneous immune complex vasculitis. Mast cell chymase degrades complement C3 and C3a.Heparin can influence the catalytic properties of chymase. What does this study add? Immunofluorescence staining positivity of fibrin in vasculitis cryosections decreased after pretreatment with recombinant human (rh)‐chymase for 24 h; heparin enhanced this effect.Rh‐chymase degraded the alpha‐, beta‐ and gamma‐chains of fibrinogen, while heparin enhanced the degradation of the beta‐chain.Rh‐chymase pretreatment of fibrinogen prolonged thrombin‐induced clotting time, and fibrinogen degradation products induced by rh‐chymase prolonged the clotting time of human plasma.Rh‐chymase degraded fibrin gel prepared from fibrinogen or human plasma. What is the translational message? Chymase may be a previously unrecognized endogenous fibrinolytic enzyme with anticoagulative properties.It may aid in the clearance of fibrin from vessel walls in aged vasculitis lesions. Plain language summary available online Respond to this article
- Subjects
MAST cells; CIRCULATING anticoagulants; FIBRINOLYTIC agents; POLYACRYLAMIDE gel electrophoresis; FIBRIN
- Publication
British Journal of Dermatology, 2019, Vol 181, Issue 2, p296
- ISSN
0007-0963
- Publication type
Article
- DOI
10.1111/bjd.17534