title: Mast cell-derived proteases control allergic inflammation through cleavage of IgE.
abstract: 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.
authors: Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
authors: Ingrid
authors: I
authors: Rauter
authors: Maria-Theresa
authors: MT
authors: Krauth
authors: Kerstin
authors: K
authors: Westritschnig
authors: Friedrich
authors: F
authors: Horak
authors: Sabine
authors: S
authors: Flicker
authors: Anna
authors: A
authors: Gieras
authors: Andreas
authors: A
authors: Repa
authors: Nadja
authors: N
authors: Balic
authors: Susanne
authors: S
authors: Spitzauer
authors: Johannes
authors: J
authors: Huss-Marp
authors: Knut
authors: K
authors: Brockow
authors: Ulf
authors: U
authors: Darsow
authors: Heidrun
authors: H
authors: Behrendt
authors: Johannes
authors: J
authors: Ring
authors: Franz
authors: F
authors: Kricek
authors: Peter
authors: P
authors: Valent
authors: Rudolf
authors: R
authors: Valenta
mesh_terms: 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*
chemical_list: D000485:Allergens; D017455:Receptors, IgE; D007073:Immunoglobulin E; D053802:Tryptases