Mast cell-derived proteases control allergic inflammation through cleavage of IgE.
BACKGROUND
Cross-linking of mast cell-bound IgE releases proinflammatory mediators, cytokines, and proteolytic enzymes and is a key event in allergic inflammation.


OBJECTIVE
We sought to study the effect of proteases released on effector cell activation on receptor-bound IgE and their possible role in the regulation of allergic inflammation.


METHODS
Using molar ratios of purified recombinant tryptase and human IgE, we studied whether tryptase can cleave IgE. Similar experiments were performed with mast cell lysates in the presence or absence of protease inhibitors. IgE cleavage products were detected in supernatants of allergen cross-linked, cultivated mast cells and in tissue fluids collected from patients' skin after IgE-mediated degranulation. The effects of protamine, an inhibitor of heparin-dependent proteases on IgE-mediated allergic in vivo skin inflammation in human subjects were studied.


RESULTS
We show that beta-tryptase, a major protease released during mast cell activation, cleaves IgE. IgE degradation products were detected in tryptase-containing tissue fluids collected from sites of allergic inflammation. The biologic significance of this mechanism is demonstrated by in vivo experiments showing that protease inhibition enhances allergic skin inflammation.


CONCLUSIONS
We suggest that IgE cleavage by effector cell proteases is a natural mechanism for controlling allergic inflammation.
Rauter
Ingrid
I
Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Krauth
Maria-Theresa
MT
Westritschnig
Kerstin
K
Horak
Friedrich
F
Flicker
Sabine
S
Gieras
Anna
A
Repa
Andreas
A
Balic
Nadja
N
Spitzauer
Susanne
S
Huss-Marp
Johannes
J
Brockow
Knut
K
Darsow
Ulf
U
Behrendt
Heidrun
H
Ring
Johannes
J
Kricek
Franz
F
Valent
Peter
P
Valenta
Rudolf
R
D000485:Allergens / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology*; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology; D017455:Receptors, IgE / Q000378:metabolism; D012867:Skin / Q000276:immunology; D053802:Tryptases / Q000378:metabolism*
D000485:Allergens; D017455:Receptors, IgE; D007073:Immunoglobulin E; D053802:Tryptases