Mast cell chymase degrades fibrinogen and fibrin

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

We aimed to study the effects of recombinant human (rh) chymase on fibrinogen, coagulation and fibrinolysis, and to relate these effects to the vasculitis pathogenesis.

Methods

The co‐localization 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 SDS‐PAGE electrophoresis and a variety of clotting and fibrin gel experiments. The effects of rh‐chymase on vasculitis cryosections were analysed by direct immunofluorescence (IF).

Results

Chymase‐positive mast cells 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 pre‐treatment 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. IF staining positivity of fibrin in vasculitis cryosections decreased after pre‐treatment 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 which may be involved in the clearance of fibrin from vessel walls in aged vasculitis lesions.

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