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Mast cell chymase degrades fibrinogen and fibrin
Author(s) -
Lipitsä T.,
Siiskonen H.,
Naukkarinen A.,
Harvima I.T.
Publication year - 2019
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.17534
Subject(s) - chymase , fibrin , tryptase , fibrinogen , chemistry , mast cell , pathology , immunology , medicine , biochemistry
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.